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PubMedDate not supplied

The effects of equivalent doses of tromethamine or sodium bicarbonate in healthy horses.

OBJECTIVE: To describe the effects of tromethamine, a putative treatment for metabolic acidosis, and to compare its biochemical effects with those of sodium bicarbonate. DESIGN: Randomized intervention study with repeated measures. ANIMALS: 16 healthy horses, 3 to 17 years old, weighing 391 to 684 kg. METHODS: Ten horses received 3 mEq/kg tromethamine and six received 3 mEq/kg sodium bicarbonate. Samples of venous blood and cerebrospinal fluid (CSF) were collected at intervals before and after drug administration. Heart rate and breathing rate were also recorded at intervals. RESULTS: Median standard base excess increased significantly (P < .05) from baseline immediately after both bicarbonate and tromethamine. These increases were not significantly different between treatments. Standard base excess returned toward baseline but remained significantly increased 3 hours after infusion of either treatment. After tromethamine, there was a significant decrease in plasma sodium concentration that lasted for at least 90 minutes. After sodium bicarbonate, no change in plasma sodium concentration was detected. Both sodium bicarbonate and tromethamine increased carbon dioxide tension in venous blood and CSF. Despite venous alkalemia, the pH of CSF decreased after both treatments. CONCLUSIONS: Tromethamine and sodium bicarbonate have similar alkalinizing ability. Tromethamine causes hyponatremia, whereas both tromethamine and sodium bicarbonate increase carbon dioxide tension in venous blood and CSF. CLINICAL RELEVANCE: If hyponatremia, hypercarbia, and acidosis of the CSF occur after tromethamine is given to horses with existing metabolic acidosis, some of the potential advantages of tromethamine may prove theoretical rather than practical.

Acid-Base Equilibrium↗

PubMed1998

Single-dose treatment of acute cystitis with fosfomycin tromethamine.

OBJECTIVE: To review the clinical pharmacology of fosfomycin tromethamine, a new antimicrobial agent for the treatment of uncomplicated lower urinary tract infections (UTIs). DATA SOURCE: Publications in English on fosfomycin, fosfomycin tromethamine, and fosfomycin trometamol (MEDLINE, 1970-1997), as well as unpublished studies submitted to the Food and Drug Administration (FDA), were reviewed. STUDY SELECTION: Comparative, randomized, controlled studies were used to analyze the efficacy and safety of fosfomycin tromethamine. DATA SYNTHESIS: Fosfomycin tromethamine is an oral antimicrobial indicated for the treatment of uncomplicated lower UTIs. This agent is active in the urine against common uropathogens that are associated with cystitis in women, including organisms resistant to other antibiotics. A single dose of fosfomycin tromethamine is well absorbed and produces therapeutic concentrations in the urine for 2-4 days. Comparative clinical trials suggest that a single dose of fosfomycin tromethamine 3.0 g is as clinically effective as 7- to 10-day treatment regimens of standard agents used to treat UTIs, such as nitrofurantoin, norfloxacin, and trimethoprim/sulfamethoxazole. Fosfomycin tromethamine is well tolerated and appears safe to use during pregnancy. CONCLUSIONS: Fosfomycin tromethamine is the only antimicrobial to be approved by the FDA for single-dose therapy in women with acute cystitis. It is as effective and safe as multidose comparators and appears safe to use during pregnancy. The acquisition cost of this new drug will need to be weighed against the improved compliance and convenience associated with its use in the treatment of uncomplicated UTIs.

Acute Disease↗

PubMed1988

Comparative pharmacokinetics of tromethamine fosfomycin and calcium fosfomycin in young and elderly adults.

The pharmacokinetics of two oral forms of fosfomycin, tromethamine (trometamol) salt and calcium salt, were studied in five young (age, 29 +/- 3 [standard deviation] years) and eight elderly (age, 72 +/- 6 years) adults. The subjects received a single 40-mg/kg (body weight) (approximately equal to 3-g) calcium fosfomycin dose and a 25-mg/kg (approximately equal to 2-g) tromethamine fosfomycin dose in fosfomycin acid form. Blood and urine samples were collected for 24 h. Antibiotic concentrations in serum and urine were measured by microbiological assay. In all subjects, the peak levels of the calcium salt in serum were two- to fourfold lower than those of the tromethamine salt (6 to 7 and 18 to 22 micrograms/ml, respectively), indicating poor intestinal absorption of the calcium form. The elimination half-life of the two oral forms was about 5 h in young adults, and the half-life was only moderately longer in elderly subjects, with large individual variations: 8.28 +/- 5.51 h for tromethamine fosfomycin and 11.80 +/- 6.86 h for calcium fosfomycin. In elderly subjects, absorption of the tromethamine salt form was not modified, but the time to peak level was delayed for the calcium salt (2.58 +/- 0.54 h versus 1.41 +/- 0.67 h in young adults). Pharmacokinetic elimination of the two forms of fosfomycin was only moderately affected in elderly subjects; we observed lower urinary elimination, about 58 versus 28% of the dose in 24-h urines for the tromethamine salt and decreased renal clearance of both forms. However, the dosages of tromethamine and calcium fosfomycin need not be adjusted for elderly subjects who have endogenous creatinine clearances above 50 ml/min per 1.73 m2.

Adult↗

PubMed2004

Antinociceptive and neurotoxicologic screening of chronic intrathecal administration of ketorolac tromethamine in the rat.

UNLABELLED: Many drugs are tested intrathecally to investigate alternatives to opioids. We aimed to explore the analgesic and possible neurotoxic effects of chronic intrathecally-administered ketorolac tromethamine in rats. Catheters were placed via atlantoaxial interval in 28 Wistar rats under anesthesia of intraperitoneally-injected thiopental 30 mg/kg. Rats were randomized into 4 groups and administered 4 repeated intrathecal doses of therapy with 5-day intervals. The control group received 10 microL of saline, and the other groups received 50, 150, and 400 microg of ketorolac tromethamine respectively. The formalin test, behavioral test, and histopathological examination of four different spinal cord levels were performed. Neither behavioral testing nor histopathological examination revealed abnormalities that would suggest neurotoxicity. Formalin tests showed that both phase I and phase II responses of ketorolac tromethamine groups were significantly less than those of the control group. Although phase I responses did not differ during comparisons among ketorolac tromethamine-administered groups, phase II responses decreased significantly in groups that received 150 and 400 microg of ketorolac tromethamine. Intrathecally administered ketorolac tromethamine reduced nociceptive responses and exhibited no untoward neurological effect even at large doses. However, its intrathecal use as a safe alternative drug for chronic pain remains to be investigated in other species. IMPLICATIONS: The present study is unique because it has demonstrated that chronic intrathecal administration of ketorolac tromethamine in rats, even at considerably large doses, showed a potent analgesic effect during the formalin test without exhibiting any neurotoxic side effect.

Analgesics↗

PubMed1997

Fosfomycin tromethamine. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections.

Fosfomycin tromethamine is a phosphonic acid bactericidal agent with in vitro activity against most urinary tract pathogens. It is particularly active against Escherichia coli, and Citrobacter, Enterobacter, Klebsiella, Serratia and Enterococcus spp. There appears to be little cross-resistance between fosfomycin and other antibacterial agents, possibly because it differs from other agents in its general chemical structure and site of action. In its new formulation as the oral tromethamine salt, fosfomycin has 34 to 41% oral bioavailability, has a mean elimination half-life of 5.7 hours, and is primarily excreted unchanged in the urine. Following a single 3 g oral dose, peak urinary concentrations occur within 4 hours and remain high (> 128 mg/L) for 24 to 48 hours, which is sufficient to inhibit most urinary tract pathogens. In clinical trials in patients with acute uncomplicated lower urinary tract infection, single-dose fosfomycin tromethamine therapy was effective, and comparable with several other antibacterial agents given either as single-dose or multiple-dose treatments [e.g. beta-lactam and fluoroquinolone agents, cotrimoxazole (trimethoprim-sulfamethoxazole), nitrofurantoin and pipemidic acid]. Bacteriological eradication rates of 75 to 90% were achieved 5 to 11 days after therapy, with eradication rates of 62 to 93% 4 to 6 weeks after therapy. In 3 large double-blind comparisons with ciprofloxacin, cotrimoxazole and nitrofurantoin, 99% of fosfomycin tromethamine recipients and 100% of patients receiving comparator agents were considered clinically cured or improved after therapy. Fosfomycin tromethamine is well tolerated, with a low incidence of adverse events. These comprise mainly gastrointestinal symptoms that are transient, mild and self-limiting. Thus, fosfomycin tromethamine achieves high clinical and bacteriological cure rates in patients with acute uncomplicated lower urinary tract infection and is well tolerated. The single-dose administration regimen and favourable US pregnancy category rating of fosfomycin tromethamine should also encourage its use in this indication.

Acute Disease↗

PubMed1983

In vitro action of combinations of antimicrobial agents and EDTA-tromethamine on Escherichia coli.

Combinations of EDTA-tromethamine and 7 antimicrobial agents [chloramphenicol, nalidixic acid, oxytetracycline, penicillin, polymyxin B, streptomycin, and triple sulfa (sulfamethazine, sulfapyridine, and sulfathiazole]) were tested for synergistic activities against Escherichia coli. Three in vitro tests were used including minimal inhibitory concentrations of the drugs, a 2-dimensional microtiter checkerboard technique, and bacterial inhibition studies. A strong synergistic inhibitory action was observed with combinations of EDTA-tromethamine plus penicillin and EDTA-tromethamine plus oxytetracycline. Combinations of EDTA-tromethamine plus chloramphenicol also had a synergistic action, but to a lesser extent than that with penicillin and oxytetracycline. When streptomycin or nalidixic acid was mixed with EDTA-tromethamine, a slight synergistic action was noticed. There was no synergistic effect recorded with combinations of EDTA-tromethamine and triple sulfa. Combinations of EDTA-tromethamine and polymyxin B had an antagonistic effect.

Animals↗

PubMed1993

WY-50,295 tromethamine, a novel, orally active 5-lipoxygenase inhibitor: biochemical characterization and antiallergic activity.

WY-50,295 tromethamine demonstrates significant 5-lipoxygenase inhibitory activity with IC50 values ranging from 0.055 microM in rat peritoneal exudate cells, to 0.16 microM in mouse macrophages, 1.2 microM in human peripheral neutrophils and 8.1 microM in rat blood leukocytes. This activity appeared selective for 5-lipoxygenase as concentrations up to 10 microM in rat peritoneal exudate cells, and 1 microM in mouse macrophages did not effect prostaglandin generation. In non-cellular enzyme assays, WY-50,295 tromethamine displayed inhibitory activity against a soluble 5-lipoxygenase from guinea pig peritoneal exudate cells (IC50 = 5.7 microM), while it was essentially inactive against 12-lipoxygenase, 15-lipoxygenase, or prostaglandin H synthetase at concentrations up to 500 microM, or against human phospholipase A2 at concentrations up to 50 microM. In purified human blood neutrophils the inhibitory activity was reversible but did not appear dependent upon substrate concentration. IN contrast, in the guinea pig cell-free 5-lipoxygenase assay changing the arachidonic acid substrate concentration from 5 to 500 microM produced a concentration-dependent reduction in inhibitory activity. WY-50,295 tromethamine inhibited the release of peptidoleukotrienes from fragmented guinea pig lung with an IC50 of 0.63 microM. When administered p.o. with a 4 h pretreatment time, WY-50,295 tromethamine inhibited ex vivo leukotriene B4 production in rat blood leukocytes with an ED50 of 19.6 mg/kg. Against an ovalbumin-induced leukotriene dependent bronchoconstriction in anesthetized sensitized guinea pigs, WY-50,295 tromethamine inhibited the ovalbumin-induced bronchoconstriction with an i.v. ED50 of 2.5 mg/kg (5 min pretreatment) and a p.o. ED50 of 7.3 mg/kg (4 h pretreatment). Significant activity was also evident with an 18 h pretreatment. Thus WY-50,295 tromethamine is an potent and selective 5-lipoxygenase inhibitor in a number of in vitro systems. Additionally the compound is orally efficacious and has a long duration of action in an allergic bronchoconstriction model. This data suggests that WY-50,295 tromethamine may have utility in the treatment of asthma and other leukotriene-dependent pathologies.

Administration, Oral↗

PubMed1995

Effects of lysine clonixinate and ketorolac tromethamine on prostanoid release from various rat organs incubated ex vivo.

The release of prostanoids from rat brain, gastric mucosa, lungs and kidneys incubated ex vivo has been investigated for up to 5 h after oral administration of 10 mg/kg lysine clonixinate or 1 mg/kg ketorolac tromethamine. Additionally, 60 min after drug administration, a time point of near-maximal inhibition of prostanoid release, the effects of 2.5, 10 and 30 mg/kg lysine clonixinate and of 0.0225, 0.15 and 1 mg/kg ketorolac tromethamine were compared. In all organs investigated both drugs inhibited fatty acid cyclooxygenase (COX) in a dose-dependent manner, but ketorolac tromethamine was more potent and had a longer-lasting effect than lysine clonixinate. While the ID50 values for lysine clonixinate were in the same order of magnitude for all 4 organs investigated, ketorolac tromethamine exhibited some organ selectivity with a particularly high activity in the kidneys. This effect might be related to the renal toxicity of ketorolac tromethamine. On the other hand, the difference in potency was smallest in brain suggesting that inhibition of central prostanoid biosynthesis could contribute to the rapid and effective inhibition of pain by both drugs. IC50 values for inhibition of purified COX-1 and COX-2 in vitro were slightly lower for lysine clonixinate (2.4 and 24.6 micrograms/ml, respectively) than for ketorolac tromethamine (3.7 and 25.6 micrograms/ml, respectively).

6-Ketoprostaglandin F1 alpha↗

PubMed1997

In vitro transcorneal permeation of ketorolac tromethamine from buffered and unbuffered aqueous ocular drops.

In vitro transcorneal permeation of ketorolac tromethamine from 0.5% w/v solutions containing equimolar (0.02 M) concentrations of citrate (pH 6.5), phosphate (pH 6.5 and 7), citrate-phosphate (pH 7) and borate (pH 7) buffers was studied using goat cornea. Cumulative % permeation was maximum with phosphate buffered drops of pH 6.5. The effect of pH and ionic strength on permeation of ketorolac tromethamine from buffered (phosphate) drops was next investigated. Cumulative % permeation of ketorolac tromethamine from buffered drops was pH dependent being maximum at pH 4.5. Adjustment of ionic strength of drops to 0.2 resulted in decreased permeation of drug. Permeation of ketorolac tromethamine from unbuffered drops of varying pH and ionic strength 0.2 was also pH dependent and was maximum at pH 4.5. Buffered drops of pH between 4.5-5.5, ionic strength 0.2, provided better permeation of drug compared to unbuffered drops of same pH and ionic strength. Above pH 6.5 unbuffered drops showed better permeation than buffered drops. Increase in molarity of phosphate buffer (pH 4.5) used in making drops, between 0 to 0.15 M increased permeation. Aqueous drops of ketorolac tromethamine formulated in 0.15 M phosphate buffer of pH 4.5 and ionic strength 0.2 showed maximum cumulative % permeation in vitro. Considering lacrimation induced drug loss in vivo, by buffer of high concentration, ketorolac tromethamine drops formulated in buffer of low molarity, pH 4.5 and ionic strength 0.2 appear suitable.

Animals↗

PubMed1985

Inhaled lodoxamide tromethamine in the treatment of perennial asthma: a double-blind placebo-controlled study.

The efficacy of lodoxamide tromethamine in the treatment of asthma was studied in a 16-week double-blind, placebo-controlled study of 68 perennial allergic subjects with asthma. Patients received either lodoxamide tromethamine, 0.25 mg four times daily, or placebo, administered by metered-dose inhaler. Response to treatment was assessed by analyzing changes in asthma symptoms, inhaled bronchodilator requirements, and pulmonary function when compared to a 2-week baseline period. Patients treated with lodoxamide tromethamine demonstrated an improvement in daytime breathing difficulty, cough, sputum production, and sleep (p less than 0.01 to 0.05), but improvement was not significantly different from that demonstrated by placebo-treated patients. Patients from both treatment groups were able to reduce their inhaled bronchodilators (p less than 0.01), but again no significant difference was apparent between lodoxamide tromethamine and placebo treatment, nor were there any differences in peak expiratory flow rate or FEV1 between the two groups. Seven patients who received lodoxamide tromethamine withdrew because of a sensation of heat and gastrointestinal symptoms. Thus, although lodoxamide tromethamine possesses potent mast cell-stabilizing activity in vitro, we have failed to demonstrate any useful long-term effect in the treatment of mild allergic asthma.

Adolescent↗

PubMed1992

Prophylactic and therapeutic carboprost tromethamine bladder irrigation in rats with cyclophosphamide-induced hemorrhagic cystitis.

Recently, prostaglandins have been shown to be effective agents for the treatment of cyclophosphamide-induced hemorrhagic cystitis. Among the prostaglandins studied is carboprost tromethamine, a PGF2a analog. To determine the effectiveness of carboprost tromethamine therapy on the urothelium, we induced hemorrhagic cystitis in 81 rats. These were divided into two treatment arms. One arm was treated prophylactically at the time of cyclophosphamide injection, and the other started treatment only after hemorrhagic cystitis was established. Animals were divided equally into groups receiving 0, 0.4, 0.8, and 1.6 mg.% carboprost tromethamine in 0.9% normal saline by continuous bladder irrigation. All bladders were examined grossly for edema and hemorrhage, then histologically for mucosal ulceration, congestion, and perivascular hemorrhage. Results from the prophylactic arm, as compared to those for controls, revealed that all groups except those treated only with 0.9% normal saline had a lower incidence of hemorrhagic cystitis (p less than 0.05). In the established hemorrhagic cystitis arm, the group treated with 1.6 mg.% carboprost tromethamine showed the best response (p less than 0.05), whereas the group treated with 0.9% normal saline showed the poorest response. This study reveals that hemorrhagic cystitis in the rat model may be prevented by prophylactic continuous bladder irrigation with carboprost tromethamine, whereas established hemorrhagic cystitis may be treated effectively with intravesical instillation of carboprost tromethamine. Although the mechanism of action of this prostaglandin on the urothelium is unknown, it appears grossly and histologically to decrease ulceration, perivascular hemorrhage, and congestion in the mucosa and submucosa.

Animals↗

PubMed1993

Anti-leukotriene effects of WY-50,295 tromethamine in isolated guinea pig pulmonary tissues.

The abilities of WY-50,295 tromethamine, a 5-lipoxygenase inhibitor, to inhibit antigen-induced leukotriene (LT) release from guinea pig lung fragments, and to prevent LTD4 or antigen-induced contraction of isolated guinea pig tracheal muscle were compared with the activities of zileuton and MK-886 (two selective 5-lipoxygenase inhibitors), and LY171883 (a LTD4 receptor antagonist). In fragmented guinea pig lung, WY-50,295 tromethamine inhibited antigen-induced LT release with an IC50 of 0.63 microM, and was 4.6- and 5.2-fold more potent than zileuton and MK-886, respectively. WY-50,295 tromethamine differed from these 5-lipoxygenase inhibitors, however, in that WY-50,295 tromethamine competitively antagonized LTD4-induced tracheal contractions (pA2 = 6.06) at concentrations that inhibited LT release. LY171883 was an effective LTD4 receptor antagonist (pA2 = 6.96), that only inhibited antigen-induced LT release at higher concentrations (IC50 = 7.9 microM). WY-50,295 tromethamine almost completely inhibited antigen-induced leukotriene-dependent tracheal contractions, whereas high concentrations of zileuton, MK-886, or LY171883 produced only partial inhibition. This partial inhibition was likely to result from 'breakthrough' 5-lipoxygenase activity, because combinations of zileuton plus MK-886 or zileuton plus LY171883, were more effective than zileuton, MK-886, or LY171883 alone. The greater efficacy of WY-50,295 tromethamine in the antigen-challenged guinea pig trachea is likely to result from its combined abilities to prevent LT biosynthesis and block LTD4 receptors.

Acetophenones↗

PubMed1998

Effects of ketoralac tromethamine and indomethacin on primary and secondary bone healing. An experimental study in rats.

Ketoralac tromethamine is a new non-steroidal anti-inflammatory drug that is being used extensively as an analgesic in orthopaedic surgery, particularly for outpatient procedures. However, as with all non-steroidal anti-inflammatory drugs there have been theoretical concerns about the effect of the drug with regard to bone metabolism and healing. In the present study bone healing of femoral osteotomies was evaluated in rats given ketoralac tromethamine in comparison with two other groups of rats given indomethacin and saline (control group), respectively. Under unstable healing conditions, 3 days of medication with indomethacin significantly reduced the femoral bending moment, bending rigidity and energy expenditure compared with the control group. Such impairment of mechanical characteristics was not found during the first 3 days after osteotomy in rats given ketoralac tromethamine. There were no significant differences in mechanical properties between the three groups when healing occurred under stable conditions. Ketoralac tromethamine is a rather new NSAID that has excellent aqueous solubility and lacks tissue irritability [2]. It is, therefore, very suitable for parenteral use. Additionally, it is the most potent NSAID known, equal or superior to morphine for pain relief following orthopaedic surgery [9]. Its use has therefore become widespread as an alternative to opioid analgesics [7]. Its effects on bone metabolism and healing have, however, not been fully elucidated, and concern has been expressed about its potential effect. The present study was designed to investigate the effects of short-term administration of ketoralac tromethamine on bone healing under stable and unstable conditions in rats, as compared to indomethacin.

Analysis of Variance↗

PubMedDate not supplied

Results of a survey of patients with ocular allergy treated with topical ketorolac tromethamine.

Exposure of the eye to airborne particles in patients predisposed to allergy often results in the signs and symptoms of allergic conjunctivitis such as red, itchy eyes and ocular discharge. The mediators of these allergic symptoms include histamine, inflammatory substances such as prostaglandins, and other products of arachidonic acid metabolism (ie, leukotrienes). Ketorolac tromethamine is a nonsteroidal anti-inflammatory agent that inhibits the activity of cyclooxygenase, one of the two major enzymes responsible for the conversion of arachidonic acid to inflammatory substances. A multicenter patient survey was performed to evaluate the effectiveness of topical ketorolac tromethamine in treating the symptoms of allergic conjunctivitis. After ocular administration of ketorolac tromethamine, 90% (246/272) of patients reported that their eyes felt better. Eighty-four percent (173/206) of respondents rated ketorolac tromethamine as good to excellent in relieving their overall symptoms of ocular allergy, and 86% (217/251) of patients found the study drug produced good to excellent relief of their ocular itching usually within minutes to 1 hour of administration. Results of this survey found ketorolac tromethamine is effective in relieving ocular itching, the hallmark symptom of allergic conjunctivitis. In addition, these results provide further evidence that the products of arachidonic acid metabolism contribute to the symptoms of allergic conjunctivitis.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1990

Compatibility of ketorolac tromethamine injection with common infusion fluids and administration sets.

The compatibility of ketorolac tromethamine injection with commonly used i.v. infusion solutions and administration set components was evaluated. The infusion solutions tested were 0.9% sodium chloride injection, 5% dextrose injection, 0.9% sodium chloride and 5% dextrose injection, Plasma-Lyte A pH 7.4 injection, Ringer's injection, and lactated Ringer's injection. The ketorolac tromethamine admixture concentration studied was 30 mg/50 mL for all solutions. Admixtures were stored in polyvinyl chloride bags and glass bottles at room temperature under fluorescent light and sampled at 0, 6, 24, and 48 hours. Chemical compatibility was determined by high-performance liquid chromatography, and physical compatibility was determined by visual analysis, counting of subvisible particles by HIAC, and pH measurements. Adsorption of ketorolac tromethamine to i.v. administration set components was also evaluated. Ketorolac tromethamine exhibited excellent physical and chemical stability in all six infusion solutions tested. No degradation of drug, formation of particulates, or adsorption to containers or infusion tubing was noted at any concentration for any of the solutions. After the solutions were mixed, the pH remained essentially unchanged. Ketorolac tromethamine injection was physically and chemically stable when mixed with a variety of commonly used infusion solutions and was not adsorbed to administration set components or to glass or polyvinyl chloride containers.

Chemistry, Pharmaceutical↗

PubMed1988

Effects of tromethamine and sodium bicarbonate buffers during cardiac resuscitation.

The effects on cardiac resuscitability of iso-osmolal solutions of tris-hydroxymethyl-aminomethane (tromethamine), sodium bicarbonate (NaHCO3) and sodium chloride placebo were compared in 30 domestic pigs using a well-established model of electrically induced cardiac arrest and resuscitation. We hypothesized that a carbon dioxide (CO2) consuming buffer like tromethamine would reduce and sodium bicarbonate would increase the respiratory acidosis of mixed venous blood, which had recently been demonstrated in our laboratory, Tromethamine did decrease and sodium bicarbonate did increase both arterial and mixed venous CO2 during cardiopulmonary resuscitation (CPR). Both concentrations of end-tidal CO2 and coronary venous PCO2 were significantly lower after tromethamine than after bicarbonate. However, tromethamine produced an unexpected vasodilator effect with reduction of mean aortic and coronary perfusion pressures to levels that are known to reduce resuscitability and survival independently of its buffer action. Neither resuscitability nor survival was altered by bicarbonate therapy in comparison with sodium chloride placebo.

Acid-Base Equilibrium↗

PubMed1999

Entry of tromethamine into the cerebrospinal fluid of humans after cerebrovascular events.

OBJECTIVE: The intravenous administration of tromethamine (INN, trometamol) lowers the intracranial pressure in patients with brain edema. One postulated mechanism of action is the increase of the pH of the cerebrospinal fluid. METHODS: To study tromethamine kinetics in serum and cerebrospinal fluid, nine patients with external ventriculostomies and normal serum creatinine values received 60 mmol intravenous tromethamine (Tris 36.34%, pH 11) over 30 minutes. Serum and cerebrospinal fluid were drawn repeatedly, and concentrations were determined by HPLC. RESULTS: Maximum serum concentrations (Cmax) ranged from 211 to 426 mg/L (median, 302 mg/L). The volume of distribution was 0.34 to 0.86 L/kg body weight (median, 0.53 L/kg), and the elimination half-life in serum (t1/2beta) 3.22 to 8.44 hours (median, 4.53 hours). Cerebrospinal fluid Cmax values ranging from 0.68 to 34.14 mg/L (median, 3.88 mg/L) were observed 1 to 12 hours after the end of the tromethamine infusion (median, 2 hours). AUC(CSF)/AUC(S) as a measure of overall cerebrospinal fluid penetration was 0.015 to 0.46 (median, 0.068). Cerebrospinal fluid Cmax and AUC(CSF)/AUC(S) depended on the function of the blood-cerebrospinal fluid barrier. Cerebrospinal fluid t1/2 (8.52 to 14.2 hours; median, 11.2 hours) was substantially longer than the t1/2beta in serum. In vitro, cerebrospinal fluid concentrations < or =30 mg/L did not influence cerebrospinal fluid pH. CONCLUSION: Tromethamine cerebrospinal fluid concentrations will be high enough to increase the pH of the cerebrospinal fluid only at large doses and in patients with a pronounced disruption of the blood-cerebrospinal fluid barrier.

Adult↗

PubMed1993

Treatment of cyclophosphamide-induced hemorrhagic cystitis with intravesical carboprost tromethamine.

We review our experience with 18 consecutive patients who received intravesical carboprost tromethamine, an F2-alpha prostaglandin, for severe hemorrhagic cystitis following cyclophosphamide chemotherapy. Of the patients 16 were given cyclophosphamide for conditioning before bone marrow transplantation and 2 received the drug as cytotoxic therapy alone (dose range 3.6 to 15.8 gm.). All patients had severe gross hematuria that was refractory to forced diuresis and to continuous saline bladder irrigation. The intravesical prostaglandin therapy was initiated only after significant transfusion requirements (greater than 1 unit packed red blood cells per day) and/or numerous catheter manipulations for relief of clot retention. Eligible patients underwent complete clot evacuation followed by intravesical instillation of 0.4 to 1.0 mg.% carboprost tromethamine for 2 hours 4 times per day, alternating with continuous saline bladder irrigation for 2 hours. Six patients attempted an alternate protocol of 0.8 to 1.0 mg.% carboprost tromethamine given by continuous saline bladder irrigation. Complete resolution of gross hematuria occurred in 9 patients (50%). Eight patients had a partial response, with decreased transfusion requirements noted. However, complete resolution ultimately required an alternative therapy (for example formalin or urinary diversion). One patient (6%) failed to respond and required formalin therapy on day 4 of carboprost tromethamine therapy. Decreased red blood cell transfusion requirements were noted during and after therapy when compared to pretreatment values. No changes in renal or bladder function were noted during the mean followup of 17 weeks (range 1 to 64 weeks). There were 3 cases of recurrent hematuria. Side effects were limited to bladder spasm in 14 of the 18 patients (78%), with no systemic complications. The results suggest that carboprost tromethamine is a useful bedside therapy for hemorrhagic cystitis due to cyclophosphamide, and treatment appears to have minimal toxicity.

Administration, Intravesical↗