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PubMed1996

Role of tachykinins in bronchoconstriction induced by intravenous administration of bradykinin in guinea-pigs.

To elucidate the role of tachykinins in bronchoconstriction induced by intravenous administration of bradykinin (Bk), we studied the effects of FK224, a neurokinin-1 (NK1) and neurokinin-2 (NK2) receptor antagonist, on the bronchoconstriction induced by intravenous (i.v.) administration of Bk (5-100 micrograms.kg-1) in guinea-pigs. Total pulmonary resistance -(RL) was measured using a pressure-volume sensitive body plethysmograph in anaesthetized artificially ventilated guinea-pigs pretreated with atropine (1 mg.kg-1) and propranolol (1 mg.kg-1). In the control group, i.v. administration of Bk produced a dose-dependent increase in RL. In animals pretreated with FK224, bronchoconstriction induced by higher doses of Bk (10, 50 and 100 micrograms.kg-1) was significantly reduced, whilst the bronchoconstriction caused by lower doses of Bk (5 and 7.5 micrograms.kg-1) was not. Pretreatment with a combination of FK224 and indomethacin markedly inhibited the bronchoconstriction induced by each dose of Bk compared with the groups pretreated with FK224 alone. Although pretreatment with indomethacin alone significantly reduced RL at a high dose of Bk (50 micrograms.kg-1), the reduction was significantly lower than that produced by a combination of FK224 and indomethacin. These results suggest that intravenous administration of a high dose of bradykinin causes bronchoconstriction both by cyclo-oxygenase products and by release of tachykinins.

Animals↗
PubMed1991

Improvement of estradiol 17 beta-D-glucuronide cholestasis by intravenous administration of dimethylethanolamine in the rat.

The intravenous administration of dimethylethanolamine in the rat promotes a selective enrichment of liver membranes with polyunsaturated phosphatidylcholines. The effect of dimethylethanolamine pretreatment on cholestasis induced by estradiol 17 beta-D-glucuronide, a potent cholestatic agent, was assessed in this study. Dimethylethanolamine, dissolved in sodium-taurocholate was infused intravenously (0.3 mg/kg/min) for 15 hr. One group of control rats (estradiol 17 beta-D-glucuronide controls) received the bile salt only. An estradiol 17 beta-D-glucuronide bolus was then injected intravenously (10.4 mg/kg) into dimethylethanolamine-pretreated and estradiol 17 beta-D-control rats, and its effect on bile flow and biliary lipid secretion was compared for 3 hr. The estradiol 17 beta-D-glucuronide inhibitory effect on bile flow and biliary lipid secretion was significantly antagonized by dimethylethanolamine pretreatment. The maximum inhibition of bile flow was found 30 min after estradiol 17 beta-D-glucuronide administration, when it decreased from 3.5 +/- 0.4 microliters/min/100 gm (basal) to 0.9 +/- 0.3 microliters/min/100 gm in estradiol 17 beta-D-glucuronide controls, whereas in dimethylethanolamine-pretreated rats this decreased only from 3.2 +/- 0.4 (basal) to 2.3 +/- 0.4 microliters/min/100 gm. Bile flow and the biliary secretion of cholesterol, phosphatidylcholine and bile salts were significantly higher in the dimethylethanolamine-pretreated rats than in estradiol 17 beta-D-glucuronide controls (p less than 0.02) during the cholestatic phase. The inhibitory effect of estradiol 17 beta-D-glucuronide on bile flow was associated with a marked decrease of membrane fluidity (p less than 0.001) assessed by 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy and with a cholesterol enrichment of microsomes, sinusoidal and canalicular liver plasma membranes and inhibition of sinusoidal Na+,K(+)-ATPase activity (p less than 0.05). These membrane alterations persisted 180 min after estradiol 17 beta-D-glucuronide administration despite complete normalization of bile flow. Dimethylethanolamine pretreatment significantly counteracted the reduction of membrane fluidity (p less than 0.001), the cholesterol enrichment and the inhibition of Na+,K(+)-ATPase (p less than 0.05) promoted by estradiol 17 beta-D-glucuronide administration in all membrane subfractions 30 and 180 min after administration. In addition, dimethylethanolamine-pretreated rats had more polyunsaturated fatty acids in membrane phosphatidylcholine with respect to the control groups. Dilatation of canaliculi and loss of microvilli were evident in estradiol 17 beta-D-glucuronide controls 180 min after estradiol 17 beta-D-glucuronide administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Intraocular penetration of cytosine arabinoside following intravenous administration in primates.

Cytosine arabinoside was administered intravenously to three monkeys. Blood, aqueous, and vitreous specimens were collected after 30 minutes, 1 hour, 2 hours, and 3 hours. Intraocular and intravenous drug concentrations were comparable at all time points, at levels likely to be effective against human tumors. This study suggests that therapeutic intraocular concentrations of cytosine arabinoside are attained following intravenous administration in primates.

Animals↗
PubMed1995

Pharmacokinetics of sulfadimethoxine and sulfamethoxazole in combination with trimethoprim after intravenous administration to healthy and pneumonic pigs.

The pharmacokinetics of two sulfonamide/trimethoprim combinations were investigated after intravenous administration to clinically healthy pigs and to the same pigs following a challenge with Actinobacillus pleuropneumoniae toxins. Endobronchial challenge with A. pleuropneumoniae toxins resulted in fever, increased white blood cell counts and decreased water and feed consumption. Healthy, as well as febrile, pigs were given sulfadimethoxine (SDM) or sulfamethoxazole (SMX) intravenously at a dose of 25 mg/kg b.w. in combination with 5 mg trimethoprim (TMP) per kg body weight. The pharmacokinetic parameters of the sulfonamides as well as their main metabolites (acetyl sulfonamides) were not significantly different in healthy and febrile pigs. In healthy and pneumonic pigs, the mean elimination half-lives of SDM were 12.9 h and 13.4 h, respectively, those of SMX 2.5 h and 2.7 h, respectively, and those of TMP 2.8 h and 2.6 h, respectively. Distribution volumes in healthy and febrile pigs of SDM and SMX varied between 0.2 and 0.4 L/kg, and those of TMP between 1.1 and 1.6 L/kg. The mean AUC of TMP was decreased and the volume of distribution and total body clearance of TMP were increased in febrile pigs. Protein binding of the drugs and metabolites studied were not significantly changed after toxin-induced fever. The extent of protein binding of SDM, SMX and TMP was in the range 94-99%, 45-56% and 40-50%, respectively. Based on knowledge of in vitro antimicrobial activity of the drug combinations against A. pleuropneumoniae it was concluded that after intravenous administration of the dose administered (30 mg/kg of the combination preparations) to healthy and pneumonic pigs, plasma concentrations of SMX and TMP were above the concentration required for growth inhibition of 50% of A., pleuropneumoniae strains for approximately 16 h, whereas bacteriostatic plasma concentrations of SDM were still present after TMP had been eliminated from plasma. Because of similar elimination half-lives of SMX and TMP in pigs this combination is preferred to the combination of SDM with TMP.

Actinobacillus Infections↗
PubMed1996

Aminoglycoside levels in the rabbit vitreous cavity after intravenous administration.

PURPOSE: To determine the penetration of gentamicin and amikacin into the rabbit vitreous cavity after their intravenous administration. METHODS: Gentamicin (1.6 mg/kg every 8 hours) and amikacin (6 mg/kg every 12 hours) were administered intravenously to 25 rabbits that had previously had the lens and vitreous removed from 43 eyes. For each drug, ocular inflammation was induced in one group of eyes by injection of heat-killed Staphylococcus epidermidis, while the other group was maintained as a control. Samples from the vitreous cavity were taken at regular intervals for 72 hours after beginning the intravenous medications and were analyzed for drug concentrations. RESULTS: The maximum intravitreal concentration +/- SD achieved for gentamicin was 1.8 +/- 0.5 microgram/ml. The maximum intravitreal concentration for amikacin was 8.5 +/- 3.2 micrograms/ml. Inflamed eyes demonstrated higher concentrations than did those without inflammation. CONCLUSIONS: In a rabbit model with conditions optimized to enhance penetration of antimicrobials into the vitreous cavity after intravenous administration, neither gentamicin nor amikacin penetrated sufficiently to reach potentially therapeutic concentrations consistently for either Pseudomonas or S epidermidis organisms.

Amikacin↗
PubMed1991

[Study of trans-placental transport of methylamphotericin B in albino rats after intravenous administration].

Transplacental penetration of amphotericin B, an methyl derivative, was studied on rats after its intravenous administration. Microbiological and radioisotopic methods were used. When the microbiological method was applied the drug was administered on days 16 to 20 or on day 20 of pregnancy in a dose of 4 mg/kg. For extraction of the antibiotic dimethylformamide was added to the substrates. The labeled antibiotic was administered in a dose of 3.3 mg/kg on days 6 to 16 and on day 20 of pregnancy. It was noted that the antibiotic accumulated in the placenta. The accumulation was more pronounced after antibiotic use in the course doses. A significant part of the antibiotic was in the placenta in the bound state. The methyl derivative amphotericin B was not detected microbiologically in the umbilical cord serum, fetal organs and amniotic fluid. Neither was it detected by extraction with ++dimethylformamide. The labeled antibiotic was neither detected in the amniotic fluid and fetal organs during the whole observation period. Therefore, the methyl derivative amphotericin B did not penetrate through the placental barrier either in the free or bound state. The direct teratogenic action of amphotericin B, a methyl derivative, after its intravenous administration to female rats is likely possible.

Amphotericin B↗
PubMed2003

Pharmacokinetics of novel inhibitors of androgen synthesis after intravenous administration in mice.

PURPOSE: The pharmacokinetics of several new androgen synthesis inhibitors were investigated after intravenous administration in mice. The inhibitors were: 3beta-hydroxy-17-(1 H-imidazol-1-yl)androsta-5,16-diene (VN/85-1), 3beta-hydroxy-17-(1 H-1,2,3-triazol-1-yl)androsta-5,16-diene (VN/87-1), 17-(1 H-imidazol-1-yl)androsta-4,16-diene-3-one (VN/108-1) and 17-(5'-isoxazolyl)androsta-4,16-dien-3-one (L-39). METHODS: Male Balb/c mice were injected with VN/85-1, VN/87-1, VN/108-1 or L-39 at 10, 25 and 50 mg/kg doses. Blood was collected at various times after drug administration via the eye orbit. The concentrations of VN/85-1, VN/87-1, VN/108-1 or L-39 in plasma were analyzed by a reversed-phase HPLC method with UV detection. RESULTS: The plasma levels of VN/85-1, VN/87-1, VN/108-1 and L-39 declined biexponentially with terminal elimination half-lives ranging from 0.88 to 1.77 h. The terminal half-lives for VN/87-1, VN/85-1 and VN/108-1 were similar. However, the terminal half-life for L-39 was significantly longer than those for VN/87-1, VN/85-1 and VN/108-1. The systemic clearance values for the steroids ranged from 0.85 to 10.91 l/h per kg with a rank order of their clearance of L-39>VN/87-1>VN/108-1>VN/85-1. The apparent volumes of distribution at steady state for the steroids ranged from 0.58 to 18.85 l/kg with a rank order of their apparent V(ss) of L-39>VN/87-1>VN/85-1>VN/108-1. The clearance and apparent V(ss) for all four compounds were dose-independent following intravenous administration of doses up to 50 mg/kg. CONCLUSIONS: VN/85-1, VN/87-1, VN/108-1 and L-39 are rapidly cleared from the systemic circulation and display linear pharmacokinetics in mice. The information presented may be used to improve the disposition profiles and activities of the steroidal inhibitors of androgen synthesis in animal models of prostate cancer.

Algorithms↗
PubMed1980

[Clinical studies on dry filled doxycycline for intravenous administration; including one case of tsutsugamushi disease (author's transl)].

On a new dry filled doxycycline derivative for intravenous administration, some clinical studies were performed. The results obtained were summarized as follows; 1. Intravenous administration was effective in three cases of pulmonary abscess, in one case of bronchopneumonia, in one case of urinary tract infection complicated to nephrolithiasis, in one case of Mycoplasma pneumonia and in one case of tsutsugamushi disease. 2. In one case of FUO (fever of unknown origin), in one case of non-bacterial meningitis and in one case of ampicillin induced hemorrhagic colitis, from whom Klebsiella oxytoca was isolated in feces, satisfactory clinical course was observed with the drug administration. However, as it was impossible to give any comments for the causative agent of each disease, the effectiveness of the derivative was not necessarily clear. 3. Neither side effects nor abnormal laboratory finding caused by the derivative were noticed in any cases.

Adolescent↗
PubMedDate not supplied

The safety, tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients.

STUDY OBJECTIVE: To evaluate the safety, tolerability, and pharmacokinetic profile of fosphenytoin, a water-soluble phenytoin prodrug, after intramuscular and intravenous administration. DESIGN: Open-label study of intramuscular administration, and double-blind, randomized study of intravenous administration. SETTING: Six and ten hospitals throughout the United States for the intramuscular and intravenous multicenter studies, respectively. PATIENTS: Neurosurgical patients who required anticonvulsant prophylaxis or treatment. INTERVENTIONS: In the intramuscular study, 118 patients received loading doses ranging from 480-1500 mg phenytoin equivalents (PE) and daily maintenance doses ranging from 130-1250 mg PE for 3-14 days. In the intravenous study, 88 patients received fosphenytoin and 28 received phenytoin sodium for 3-14 days. Mean +/- SD loading doses and maintenance doses of intravenous fosphenytoin and phenytoin were 1082 +/- 299 mg PE and 411 +/- 221 mg PE, and 1082 +/- 299 mg and 422 +/- 197 mg, respectively. Trough phenytoin concentrations were measured daily in all patients. MEASUREMENTS AND MAIN RESULTS: Intramuscular fosphenytoin was safe and well tolerated, with no irritation found for 99% of all injection site evaluations. Adverse events associated with the drug occurred in 9% of patients, commonly those typical of the parent drug. For intravenous treatment, the frequency of mild irritation at the infusion site was significantly lower in the fosphenytoin group (6%) than in the phenytoin group (25%, p < 0.05). Reductions in infusion rates were required in 17% and 36% of fosphenytoin and phenytoin recipients, respectively. No significant difference was observed relative to adverse events or seizure frequency between the groups. Trough plasma phenytoin concentrations were approximately 10 micrograms/ml or greater in patients receiving at least 3 days of intramuscular and intravenous fosphenytoin. Trough phenytoin concentrations were similar between patients receiving intravenous phenytoin and fosphenytoin on all study days. CONCLUSION: Fosphenytoin can be administered intramuscularly and intravenously in neurosurgical patients to achieve and maintain therapeutic phenytoin concentrations for up to 14 days. Both routes are safe and well tolerated. Intravenous fosphenytoin is significantly better tolerated than intravenous phenytoin sodium in this patient subset.

Adolescent↗
PubMed2001

Intravenous administration of ecstasy (3,4-methylendioxymethamphetamine) enhances cortical and striatal acetylcholine release in vivo.

The effect of intravenous administration of 3,4-methylendioxymethamphetamine (MDMA), in a range of doses (0.32-3.2 mg/kg) that have been shown to maintain self-administration behaviour in rats, on in vivo acetylcholine release from rat prefrontal cortex and dorsal striatum was studied by means of microdialysis with vertical concentric probes. Intravenous administration of MDMA dose-dependently increased basal acetylcholine release from the prefrontal cortex to 57+/-21%, 98+/-20%, 102+/-7% and 141+/-14% above baseline, at doses of 0.32, 0.64, 1.0 and 3.2 mg/kg, respectively. MDMA also stimulated striatal acetylcholine release at the dose of 3.2 mg/kg i.v. (the maximal increase being 32+/-3% above baseline) while at the dose of 1 mg/kg i.v., MDMA failed to affect basal acetylcholine output. Administration of MDMA also dose-dependently stimulated behaviour. The results of the present study show that MDMA affects measures of central cholinergic neurotransmission in vivo and suggest that at least some of the psychomotor stimulant actions of MDMA might be positively coupled with an increase in prefrontal cortical and striatal acetylcholine release.

Acetylcholine↗
PubMed1996

Pharmacokinetics of ethinyloestradiol in rabbits after intravenous administration.

The pharmacokinetics of ethinyloestradiol (EE2) after intravenous administration of 30, 50 and 100 micrograms.kg-1 was investigated in rabbits. A high-performance liquid chromatographic (HPLC) method with electrochemical (EC) detection was used to measure EE2 in plasma samples in order to avoid the interferences of natural oestrogens. After compartmental analysis, the disposition of EE2 was well described by a two-compartmental open model with mean values of: alpha = 0.3448 +/- 0.2922, 0.1965 +/- 0.1755, 0.3058 +/- 0.1225 min-1, and beta = 0.0137 +/- 0.0018, 0.0140 +/- 0.0065, 0.0198 +/- 0.0066 min-1, for the three doses studied, respectively. There were no dose-related differences (ANOVA, P < 0.05) in a, b or Vss, but significant differences were detected in clearance (90.9 +/- 18.7; 80.6 +/- 17.6; 116.3 +/- 21.5 ml.min-1.kg-1) between the 100 micrograms.kg-1 group and lower dose groups. The AUC increased significantly with the doses (341.7 +/- 67.1; 645.8 +/- 143.9; 892.2 +/- 211.9 ng.min.ml-1). After non-compartmental analysis there were no significant differences in lambda, MRT or Vss as a function of dose, but these differences were significant when Cl or AUC were compared. There were no significant differences in AUC or Cl values obtained by compartmental and non-compartmental analysis.

Animals↗
PubMed1986

Characterization of a translational inhibitor isolated from rabbit brain following intravenous administration of d-lysergic acid diethylamide.

Intravenous administration of d-lysergic acid diethylamide (LSD) to rabbits results in a transient inhibition of brain protein synthesis in vivo and in vitro. A translational inhibitor that appears in the postribosomal supernatant fraction of cerebral hemispheres following LSD administration was partially purified by gel filtration on Sephadex G-150 and precipitation with 60% ammonium sulfate. This inhibitor, which was proteinaceous, reduced the translational capacity of an initiating cell-free protein synthesis system derived from brain. It also inhibited a messenger RNA-dependent reticulocyte lysate programmed with brain polysomes and a globin-synthesizing reticulocyte lysate system. Addition of the partially purified inhibitor to a brain cell-free protein synthesis system resulted in the decreased formation of ternary complexes as well as 40 and 80S initiation complexes, suggesting that the inhibitor affects an early step in the initiation of protein synthesis in brain.

Animals↗
PubMed1988

[Two cases of obstructive jaundice due to advanced gastric cancer with marked response to the intravenous administration of cisplatinum].

Two cases of obstructive jaundice due to advanced gastric cancer were treated with intravenous administration of cisplatinum. The first case was a 46-year-old female who had undergone gastrojejunostomy 5 months earlier because of Borrmann type 3 gastric cancer. The tumor involved the head of the pancreas and a portion of the duodenum with distant intraperitoneal dissemination (S3N3P3H0). She was admitted to Shimodate Municipal Hospital on June 8 because of abdominal pain and jaundice. Her abdomen was distended with ascites, and there was a fist-sized tumor in the lower portion. CT examination revealed that the jaundice was caused by obstruction due to the main tumor. Histologically, the tumor consisted of poorly differentiated adenocarcinoma. Intravenous administration of CDDP (50 mg/body/week X 4), MMC (4 mg/body/week X 4) and FT (400 mg/body/day for 4 weeks) was carried out. After the chemotherapy, the jaundice, abdominal pain and ascites disappeared, and the abdominal tumor had markedly reduced in size which was regarded as PR. The second case was 66-year-old male who had received subtotal gastrectomy and transverse colectomy 16 months ago because of Borrmann type 3 gastric cancer. The tumor comprised well-differentiated adenocarcinoma and infiltrated to the mesentery of the transverse colon with positive lymphnodes (S3N1P1H0, stage IV). This time he was admitted to the hospital because of general fatigue and jaundice. According to CT examination, the common bile duct was obstructed by metastasized lymphnode around the pancreas. He had elevated serum level of total bilirubin (7.7 mg/gl) and CA 19-9 (23,000 U/ml). After the administration of CDDP (50 mg/body/week X 4) and MMC (4 mg/body/week X 4), his complaints disappeared and the serum total bilirubin level and CA 19-9 level returned within normal range. These data suggest that combination chemotherapy using CDDP was effective in these 2 cases.

Adenocarcinoma↗
PubMed1994

Glucagon stimulates GH secretion after intramuscular but not intravenous administration. Evidence against the assumption that glucagon per se has a GH-releasing activity.

In order to verify the true GH-releasing effect of glucagon and to explain the mechanism underlying this effect, we studied the effect of glucagon (GLU, 1 mg) administered either iv or im on both basal and GHRH (1 microgram/kg)-induced GH rise in 48 normal short children and adolescents. Moreover, the in vitro effect of GLU on rat anterior pituitary cells was studied. Intravenous administration of GLU induced no significant GH rise. On the other hand, im GLU administration induced a clear-cut GH increase (mean +/- SE GH peak after GLU vs placebo = 25.7 +/- 3.9 vs 10.1 +/- 3.6 micrograms/L, p < 0.01). Intravenous administration of GLU failed to modify the GHRH-induced GH rise either when coadministered with the neurohormone (35.2 +/- 4.1 vs 34.1 +/- 6.0 micrograms/L) or when given 60 min earlier (20.2 +/- 5.8 vs 21.1 +/- 8.3 micrograms/L). Differently from iv GLU, im GLU strikingly potentiated the GH response to GHRH given 90 min later (57.5 +/- 6.3 vs 24.7 +/- 9.1 micrograms/L, p < 0.01). Mean plasma glucose levels increased 30 min after GLU, administered either iv or im, and returned to basal levels 60 min later. GH secretion from dispersed rat pituitary cells was unaffected by incubation with GLU (10(-10)-10(-4) mol/L). Incubation of the cells with 10(-7) mol/L GHRH induced instead a clear-cut stimulation of GH release. In conclusion, our data demonstrate that glucagon per se has not GH-releasing activity as indicated by its uneffectiveness to release GH in vitro and after intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1997

A comparison of intratracheal and intravenous administration of gentamicin during liquid ventilation.

UNLABELLED: Pulmonary absorption of aminoglycosides is poor with intravenous administration, but may be enhanced by direct intratracheal administration of these drugs using perfluorochemical liquid ventilation (LV). To test this hypothesis, gentamicin sulfate was administered to two groups of newborn lambs during LV. Serum and lung tissue levels of gentamicin were compared after either pulmonary intratracheal (IT) or intravenous (IV) routes of administration. Serial serum levels of gentamicin were obtained every 15 min for the 1st h, every 30 min for the 2nd h, and then hourly until sacrifice (maximum 6 h). At sacrifice, representative samples of each lung lobe were homogenized and analyzed for tissue gentamicin content. At 1 h, serum gentamicin levels were similar in both groups: IT administration levels were 3.7 +/- 0.55 SE micrograms/ml and IV levels were 3.5 +/- 0.85 SE micrograms/ml. The peak serum gentamicin level of 4.8 +/- 0.8 SE micrograms/ml for the pulmonary administration group occurred 1.5 h after administration. Lung tissue levels of gentamicin for IT administration (4.04 +/- 0.62 SE micrograms/g) were significantly greater than for IV administration (1.75 +/- 0.33 SE micrograms/g; P < 0.05). There were no significant differences in interlobar gentamicin distribution for either mode of administration. CONCLUSION: Perfluorochemical can be used as a vehicle for intratracheal delivery of antimicrobials. This route provides equivalent serum levels at 1 h, higher lung tissue levels, and uniform interlobar distribution relative to intravenous administration of gentamicin. We speculate that pulmonary administered gentamicin during LV may provide an effective alternative treatment modality in the management of severe neonatal pneumonia.

Administration, Inhalation↗
PubMed1996

Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after single-dose oral and intravenous administration.

A randomized, crossover study of 12 healthy volunteers was conducted with single, 1.5-g doses of mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), after oral and intravenous administration. During the intravenous infusion, phase systemic plasma clearance of MMF was approximately 10 L/min and the half-life (t1/2) was a few minutes. After oral administration, however, plasma MMF was below quantitation limits at all times. The plasma MPA profile of oral MMF showed a sharp peak at approximately 1 hour and a secondary peak at 8 to 12 hours. Mean apparent plasma t1/2 of MPA was similar for both routes (approximately 17 hours). The area under the concentration-time curve (AUC) from time 0 to 24 hours was statistically higher for intravenous than for oral administration, but total AUC showed statistical equivalence (80-120 rule), with mean bioavailability of MPA from oral administration of MMF estimated as 94.1% relative to the intravenous route. Total plasma AUC of mycophenolic acid glucuronide (MPAG), the sole metabolite of MPA, was four- to five-fold higher than MPA. Total 48-hour MPAG recovery in urine was statistically equivalent for the two routes and represented a mean of 70% of administered drug; corresponding MPA recovery was less than 1%. Renal clearance (ClR) values required transport mechanisms for MPAG, but not for MPA. The ClR of MPAG was statistically higher after intravenous administration than oral administration. MMF administered orally undergoes rapid, complete absorption and essentially complete presystemic deesterification. There was presystemic removal of MPA, but enterohepatic circulation compensated for the first pass loss. Renal metabolism of MPA also may have occurred.

Administration, Oral↗
PubMed2001

Responsiveness to intravenous administration of salbutamol in chronic obstructive pulmonary disease patients with acute respiratory failure.

OBJECTIVE: In chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF), bronchodilating agents administered by inhalation have, in general, little effect on dynamic hyperinflation and concurrent static intrinsic positive end-expiratory pressure (PEEPi,st). Since in COPD the severely obstructed segments of the lung may not be reached by inhaled medication, we reasoned that drug efficiency may be enhanced by intravenous administration of the agent. DESIGN: Physiological study. SETTING: Two four-bed surgical-medical ICUs of a university hospital. PATIENTS: Fourteen COPD patients were studied within 36 h from the onset of ARF. MEASUREMENTS AND RESULTS: Static compliance (Cst,rs), minimal (Rmin,rs) and additional (DeltaRrs) resistance of the respiratory system, and PEEPi,st were measured before and after intravenous administration of salbutamol. All patients had limitation of air flow before and after salbutamol administration. On average, after salbutamol there was a small, though significant, decrease in Rmin,rs (-9%), DeltaRrs (-12%) and PEEPi,st (-8%). CONCLUSION: The changes in resistance and PEEPi,st after intravenous administration of salbutamol were too small to be of clinical significance.

Acute Disease↗