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Results for “randomized crossover trial”

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At least 613 records · Page 34Linked to original sources

PubMed2004

Double-blind comparative study of the action of repeated administration of milnacipran versus placebo on cognitive functions in healthy volunteers.

OBJECTIVE: The principal objective was to compare the effects of milnacipran, an antidepressant characterized by a dual-action on serotonin and noradrenaline reuptake, with placebo on memory, attention and psychomotor performance in healthy volunteers. The secondary objective was to evaluate the effects of milnacipran on mood, anxiety and vigilance in these subjects. METHODS: In a double-blind crossover randomized trial, milnacipran (50 mg b.d.) or placebo was administered during two periods of 7 days separated by a washout period of 7 days. Memory tests (recall of words, images and coloured bars), tests to evaluate attention and vigilance (squares test, critical flicker fusion test and choice reaction time test) and visual analogue scales for affect and sleep were used. RESULTS: There were no significant differences between milnacipran and placebo groups with respect to the psychomotor functions tested. No differences were observed in the Norris scales for vigilance, anxiety or satisfaction or in the sleep questionnaire (sleep latency, sleep quality and waking). CONCLUSION: Milnacipran, administered at 100 mg per day for 7 days to healthy volunteers, had no effects on cognitive functions.

Adult↗

PubMed1995

Intranasal insulin therapy: the clinical realities.

To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycaemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosa physiology was unaffected after intranasal insulin. We conclude that due to low bioavailability and to a high rate of therapeutic failure, intranasal insulin treatment is not a realistic alternative to subcutaneous insulin injections at the present time.

Administration, Intranasal↗

PubMed1995

Effects of zamic as a means for zinc supplementation in growing children.

We investigated the effects of zinc supplementation in case of moderate growth retardation in which GH treatment could not be used. Zamic (ZA, an association containing arginine, L-methionine, and zinc; from Aguettant pharmaceuticals) was compared with arginine aspartate (AA) (5 g) in a crossover randomized trial (6 mo of each treatment at random order over 1 yr). We present preliminary results of 24 children who completed the study (3 girls, 21 boys, age 9-13 yr). Subjects had to be prepubertal, with no GH deficiency diagnosed. In 15 subjects growth velocity was lower than 5 mm/mo: In this case ZA improved growth velocity (rising from 3.105 +/- 0.229 to 5.4 +/- 0.69 mm/mo p < 0.01), whereas the effect of AA was not significant. The increase in growth velocity was higher with ZA (+2.44 +/- 0.657 mm/mo) than AA (+0.438 +/- 0.450 mm/mo) p < 0.05. These results suggest that ZA is more efficient than AA, consistent with the hypothesis that zinc needs are increased in those children in this period of life.

Adolescent↗

PubMed1997

Comparative topical anaesthesia of EMLA and liposome-encapsulated tetracaine.

BACKGROUND: The eutectic mixture of local anaesthetics (EMLA) provides effective topical anaesthesia after a minimum of 60 to 90 min application. Since liposome-encapsulated tetracaine (LET) can provide rapid dermal penetration, the goal of this study was to compare the local anaesthetic effects of EMLA and LET in human volunteers after 60 min application. METHODS: After obtaining institutional approval and informed consent, healthy volunteers were recruited in a double blind, crossover, randomized trial. The study creams (0.5 ml EMLA and 0.5 ml LET 5%) were applied randomly to opposite arms for 60 min. The discomfort of i.v. catheterization was assessed using a visual analogue pain score (VAS). Cutaneous side effects of the creams were recorded. RESULTS: Sixty-one subjects were studied. Twenty-one were excluded because of technical difficulties. Forty subjects completed the study and were included in the data analysis. The mean ( +/- SD) VAS was lower for LET than for EMLA (10.9 +/- 9.0 mm vs 22.7 +/- 17.1 mm, P < 0.001). Erythema secondary to vasodilatation occurred more frequent in the LET group than in the EMLA group (33 vs 3, P < 0.001). One subject with a history of atopy developed a rash at the LET application site. CONCLUSION: Liposome-encapsulated tetracaine can provide a more effective topical anaesthesia than EMLA for intravenous catheterization after 60 min application. Clinical evaluations are necessary to determine the efficacy and safety of LET in providing topical anaesthesia for various invasive percutaneous procedures in other patient populations.

Administration, Topical↗

PubMed1993

Ziskind-Somerfeld Research Award 1993. Biochemical, behavioral, and clinical studies of the role of inositol in lithium treatment and depression.

Lithium (Li) reduces brain inositol levels by inhibiting the enzyme inositol monophosphatase. The enzyme inositol-1-phosphatase was measured in human red blood cells of controls, Li-free bipolar patients, and Li-treated bipolar patients and was found to be reduced by 80% in Li-treated bipolars, thus supporting the concept that chronic Li at therapeutic concentrations inhibits this enzyme. Two behaviors in rats caused by Li, reduction of rearing, and Li-pilocarpine seizures, are reversed by intracerebroventricular replenishment of inositol. The reversal is stereospecific to the naturally occurring myo-inositol; whereas the stereoisomer L-chiro-inositol is ineffective. The reversal is dose-dependent, requiring a dose consistent with known quantities of brain inositol depletion; and is time-dependent, as inositol must be given 1-8 h before stimulation. High-dose peripheral inositol also reverses the limbic seizures induced by Li-pilocarpine, and using gas chromatography was shown to increase brain inositol levels that had been reduced by Li treatment. Low-dose inositol could be shown to reverse a peripheral Li-induced side effect, polyuria/polydipsia, in rats and in patients treated with Li. A higher dose of inositol markedly reduced Hamilton Depression Ratings in 9 of 11 unipolar major depressive disorder patients previously unresponsive to tricyclics, in an open design, but had no effect on chronic schizophrenics in a controlled double-blind randomized crossover trial. A new inositol monophosphatase inhibitor, a fungal product originally discovered as a complement inhibitor, was found to act like Li and lower the seizure threshold for subconvulsant doses of pilocarpine. These data suggest that inositol monophosphatase inhibition is a key mechanism of Li's therapeutic action and that design of new inositol monophosphatase inhibitors may be a practical strategy to create new compounds with Li-like therapeutic effects.

Adult↗

PubMed1998

Comparison of bromfenac and naproxen sodium in the management of primary dysmenorrhea.

Objective: To compare a new analgesic with an established standard and placebo in the treatment of primary dysmenorrhea.Methods: Bromfenac (B) 25 or 50 mg prn, up to 4 doses daily, was compared with naproxen sodium (N) (550/275 mg) and placebo (P) in a double-blind crossover randomized trial where 54 women were treated over 4 menstrual periods. Each treatment lasted up to 3 days. The first-dose analysis was based on a 6-hour observation period. Total pain relief (TOPAR) and summed pain intensity difference (SPID) scores were calculated from hourly collected data as areas under the respective time curves.Results: All 3 active treatments were superior to placebo in all summary variables (SPID and TOPAR for 3 and 6 hours) and corresponding peak pain relief and peak PID, duration of pain half-gone, and global assessment. Both B doses were superior to P in providing significant pain relief between hours 1 and 6, whereas N was superior to P at hours 1, 3, and 4. Good to excellent global rating was achieved by 74% of patients on B 50 mg, 59% on B 25 mg, 57% on N and 33% on P (P <.001) after the first dose. Patients rated the trial medication superior to their usual treatment as follows: B 50 mg: 65%, B 25 mg: 55%, N: 51%, P: 29% (P <.001). Adverse events were infrequent and not significantly different among the 4 treatments.Conclusion: Both doses of bromfenac were significantly superior to placebo and at least as efficacious as naproxen sodium in management of primary dysmenorrhea.

Journal Article↗

PubMed2006

The role of tidal peritoneal dialysis in modern practice: A European perspective.

Tidal peritoneal dialysis (TPD) has been introduced to optimize adequacy of peritoneal dialysis (PD). Early studies reported similar or even better small solute clearances with TPD than those achieved with continuous ambulatory peritoneal dialysis or continuous cyclic peritoneal dialysis. However, in many studies treatment volumes were much higher during TPD compared with other PD modalities. Based on current evidence, TPD provides no advantage of increased small solute clearances, middle molecule clearances, or peritoneal ultrafiltration as compared to non-tidal automated peritoneal dialysis (APD) when dialysate flow is kept constant. However, TPD reduces drainage pain and nightly alarms during cycler treatment. Tidal volume should be kept as high as possible in these patients, especially in those with low average peritoneal transport rates. Based on theoretical considerations and little evidence, TPD could provide better clearances than conventional APD when a very high dialysate flow (>or=5 l/h) is used. Such dialysate flow rates are not routinely prescribed in home APD patients. However, they may be interesting for in-center PD patients. One randomized crossover trial reported higher small solute clearances with TPD compared to non-tidal APD in patients with acute renal failure. TPD is also the preferred treatment modality in patients with ascites as it allows a controlled outflow of fluid from the peritoneal cavity. Newer treatment modalities, for example, continuous flow PD, may be interesting alternatives in an effort to increase efficacy of PD in the future. However, because such treatment regimens are expensive and elaborate they have not been established for routine use until now.

Dialysis Solutions↗

PubMed2000

Influence of moderate chronic wine consumption on insulin sensitivity and other correlates of syndrome X in moderately obese women.

Epidemiologic studies indicate that alcohol consumption is associated with improved insulin sensitivity; however, scant experimental evidence confirms this observation. To determine the effects of regular moderate wine consumption on insulin sensitivity, 20 overweight women (body mass index [BMI], 29.8 +/- 2.2 kg/m2) participated in a 20-week free-living randomized crossover trial. The subjects, serving as their own controls, consumed wine (190 mL red wine, 13% vol/vol ethanol, 5 days per week) for 10 weeks and abstained for 10 weeks or vice versa. The dependent variables (body weight, BMI, percent body fat, blood pressure, fasting blood glucose and insulin, blood lipids, dietary intake, and insulin sensitivity by intravenous glucose tolerance test [IVGTT]) were measured at the pretest, at the 10-week crossover, and at the 20-week completion of the study. Data were analyzed at the pretest and at completion of the wine drinking and abstention periods of the study using ANOVA by order of treatment. Fasting glucose remained unchanged (mean +/- SD; P > .05) throughout the experiment (pretest, drinking, and abstention, 91.1 +/- 9.2, 91.6 +/- 9.1, and 88.5 +/- 11.2 mg/dL), as did the measures of insulin sensitivity, fasting insulin (pretest, drinking, and abstention, 8.6 +/- 3.3, 8.6 +/- 4.1, and 9.1 +/- 4.7 microU/mg) and the insulin sensitivity index (3.60 +/- 2.96, 3.25 +/- 2.17, and 3.30 +/- 1.84). Body composition and blood lipids also remained unchanged (P > .05) during treatment. Moderate wine consumption at this dose in overweight women did not improve or impair insulin sensitivity, nor did it change any of the known correlates of insulin sensitivity, including body weight and composition, blood lipids, and blood pressure.

Adult↗

PubMed1992

Experimental study of high-frequency two-way jet ventilation.

BACKGROUND AND METHODS: A new mode of jet ventilation, high-frequency two-way jet ventilation, was devised and introduced to increase CO2 elimination. High-frequency two-way jet ventilation was achieved by adding reverse jet pulses inside the trachea through an intratracheal reverse jet system to the expiratory phase of common high-frequency jet ventilation. The ventilatory efficiency and features of high-frequency two-way jet ventilation were investigated and compared with those features of high-frequency jet ventilation in ten dogs in the same experimental condition. Random sample selection and randomized crossover trial were used for comparison between high-frequency two-way jet ventilation and high-frequency jet ventilation. Peak inspiratory pressure, end-expiratory pressure, and the arterial blood gas variables (PaO2, PaCO2, and pH) were measured during the study. RESULTS: PaCO2 with high-frequency two-way jet ventilation was about 35% lower than that with high-frequency jet ventilation (from 45 to 29 torr [6.0 to 3.9 kPa], p less than .01). Simultaneously, peak inspiratory pressure and end-expiratory pressure during high-frequency two-way jet ventilation were significantly lower than those same variables measured during high-frequency jet ventilation. End-expiratory pressure of high-frequency two-way jet ventilation was a negative pressure (-2.45 +/- 0.45 cm H2O). The pH of high-frequency two-way jet ventilation was significantly higher than that of high-frequency jet ventilation. CONCLUSIONS: Compared with high-frequency jet ventilation, high-frequency two-way jet ventilation demonstrated a ventilatory feature of increasing CO2 elimination and simultaneously decreasing airway pressure.

Animals↗

PubMed1992

Effect of experimental hemorrhagic shock on hepatic drug elimination.

OBJECTIVE: Exogenous substrates were used to measure hepatic function for the purposes of determining organ dysfunction and to evaluate the effect of experimental hemorrhagic shock with resuscitation on hepatic drug elimination. DESIGN: Prospective, controlled, non-randomized crossover trial. INTERVENTIONS: Eleven chronically instrumented immature swine were studied using a fixed-volume hemorrhage model (45 mL/kg blood removal over 15 mins) followed by resuscitation with lactated Ringer's solution at three times the volume of shed blood. One week before and immediately after hemorrhage and resuscitation, hepatic function markers (indocyanine green and antipyrine) were simultaneously administered intravenously. MEASUREMENTS: Physiologic data and blood samples were collected over 12 hrs after drug administration. Drug clearances, volumes of distribution, and half-lives were determined. MAIN RESULTS: For indocyanine green, there was no substantial change in pharmacokinetics from preshock to postshock, suggesting minimal change in hepatic blood flow. For antipyrine, clearance was decreased by 30% after shock and resuscitation (p = .05), suggesting that oxidative metabolism was acutely impaired. CONCLUSIONS: The information indicates that hepatic oxidative drug metabolism may be impaired early after hemorrhagic shock and that dosages of drugs in this class should be carefully examined when administered to patients who have sustained injury with hemorrhagic shock.

Animals↗

PubMed2001

A comparative trial of paper-and-pencil versus computer administration of the Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire.

BACKGROUND: Although most health-related quality of life questionnaires are self-administered by means of paper and pencil, new technologies for automated computer administration are becoming more readily available. Novel methods of instrument administration must be assessed for score equivalence in addition to consistency in reliability and validity. OBJECTIVES: The present study compared the psychometric characteristics (score equivalence and structure, internal consistency, and reproducibility reliability and construct validity) of the Quality of Life in Reflux And Dyspepsia (QOLRAD) questionnaire when self-administered by means of paper and pencil versus touch-screen computer. The influence of age, education, and prior experience with computers on score equivalence was also examined. RESEARCH DESIGN: This crossover trial randomized 134 patients with gastroesophageal reflux disease to 1 of 2 groups: paper-and-pencil questionnaire administration followed by computer administration or computer administration followed by use of paper and pencil. To minimize learning effects and respondent fatigue, administrations were scheduled 3 days apart. A random sample of 32 patients participated in a 1-week reproducibility evaluation of the computer-administered QOLRAD. RESULTS: QOLRAD scores were equivalent across the 2 methods of administration regardless of subject age, education, and prior computer use. Internal consistency levels were very high (alpha = 0.93-0.99). Interscale correlations were strong and generally consistent across methods (r = 0.7-0.87). Correlations between the QOLRAD and Short Form 36 (SF-36) were high, with no significant differences by method. Test-retest reliability of the computer-administered QOLRAD was also very high (ICC = 0.93-0.96). CONCLUSIONS: Results of the present study suggest that the QOLRAD is reliable and valid when self-administered by means of computer touch-screen or paper and pencil.

Age Factors↗

PubMed1995

The Influence of Misoprostol on the Adverse Renal Effects and Stereospecific Pharmacokinetics of Ibuprofen in Chronic Renal Insufficiency.

The use of nonsteroidal anti-inflammatory drugs in patients with chronic renal insufficiency (CRI) may be complicated by renal functional abnormalities due to the inhibition of renal prostaglandins. We tested the hypothesis that administration of the oral PGE1 analog, misoprostol, could attenuate the adverse renal effects of ibuprofen in patients with CRI. Because the metabolism of misoprostol and the stereoinversion of R- to S-ibuprofen involve the same metabolic pathway, the stereospecific pharmacokinetics of ibuprofen were also evaluated. In a randomized, crossover trial of six stable CRI patients (Clcr 25--67 ml min(minus sign1)), in sodium balance on a 150 mEq Na(+) per day metabolic diet, we compared the effects of ibuprofen 600 mg qid with and without misoprostol 200 &mgr;g qid upon Clcr, Clinulin, Clpah, Na(+), and K(+) excretion during 4-h clearance studies. We also assessed stereospecific ibuprofen kinetics following single dose (acute) and after 7 days on drug(s) (chronic). Daily weights, supine blood pressures, electrolytes, osmolality, BUN, creatinine and 24-h urine collections for Clcr and Na(+) and K(+) excretions were obtained during chronic dosing. Supine and upright plasma renin activities were obtained prior to dosing and during chronic dosing for both treatment limbs. Ibuprofen alone resulted in an approximately 20% transient reduction in GFR, occurring 2--2.5 h following dosing in both the acute and chronic clearance studies. This was not affected by misoprostol. There was a greater degree of stimulation of PRA with the upright posture with misoprostol plus ibuprofen than with ibuprofen alone. There was a significant weight gain in both study limbs, but no effect of misoprostol (1.2 plus minus 0.2 kg ibuprofen alone and 1.0 plus minus 0.2 kg ibuprofen plus misoprostol, p = 0.13). Otherwise no clinically significant alteration in renal function occurred in either treatment limb. The presence of misoprostol did not alter the stereospecific pharmacokinetics of ibuprofen. We conclude that misoprostol does not significantly alter the renal effects of ibuprofen in patients with mild to moderate CRI.

Journal Article↗

PubMed1996

Serum Estradiol and Estrone Levels During 3 Weeks of Alternate-Site and Same-Site Applications of a Once-A-Week Drug-in-Adhesive Transdermal Estradiol Patch.

This open-label, randomized crossover trial was conducted in healthy postmenopausal women to characterize the serum estradiol and estrone profiles from a once-a-week transdermal estradiol patch applied repeatedly to the same site or to alternate sites on the abdomen over a 3-week period. Similar mean serum estradiol and estrone profiles and circulating estradiol:estrone ratios of approximately 1.0 were observed for both patch application regimes. Repeated application to the same or alternate sites did not result in an accumulation of exogenous estradiol or in a statistically significant increase in application-site reactions. Although the once-a-week transdermal estradiol patch should be applied to alternate sites to reduce the likelihood of dermatologic reactions, accidental application site overlap should not result in an increase in serum estradiol and estrone concentrations.

Journal Article↗

PubMed2003

Which is the correct term for blood pressure measurements taken at home?

The terms 'self-blood pressure' and 'home blood pressure' are being used to describe measurements of blood pressure taken by the patients at home. However, home measurements are not always self-measurements, because these are often taken by the patients' relatives. There is little evidence on the effect of self-measurement on the level of blood pressure taken using automated electronic devices. In regard to clinic blood pressure, two studies using automated devices found no difference between measurements taken by physicians or patients themselves, irrespective of whether self-measurements were taken in the presence or the absence of the physician. In regard to home blood pressure, one randomized crossover trial showed no difference between home measurements taken by the patients themselves or their relatives using fully automated devices. On the other hand, many studies have consistently shown home blood pressure to be lower than clinic pressure. Taken together these data suggest that self-measurement has no effect on the level of blood pressure, either in the clinic, or at home. The lower level of home in comparison to clinic blood pressure seems to be exclusively attributed to the effect of the different setting, rather than the person who is taking measurements. Therefore the term 'self blood pressure' seems to be a misnomer, whereas the term 'home blood pressure' represents a more appropriate term for home measurements taken by patients or their relatives.

Blood Pressure Determination↗

PubMedDate not supplied

Lamotrigine as an add-on treatment for depersonalization disorder: a retrospective study of 32 cases.

OBJECTIVES: Depersonalization disorder (DPD) is a chronic condition characterized by the persistent subjective experience of unreality and detachment from the self. To date, there is no known treatment. Lamotrigine as sole agent was not found to be effective in a previous small double-blind, randomized crossover trial. However, evidence from open trials suggests that it may be beneficial as an add-on medication with antidepressants. METHODS: We report here an extended series of 32 patients with DPD in whom lamotrigine was prescribed as an augmenting medication. Most of the patients were receiving selective serotonin reuptake inhibitors. RESULTS: Fifty-six percent (n = 18) of patients had a more than or equal to 30% reduction on the Cambridge Depersonalization Scale score at follow-up. Both maximum dose of lamotrigine used and before treatment Cambridge Depersonalization Scale scores showed positive correlations with the percentage of response. CONCLUSIONS: The results of this trial suggest that a significant number of patients with DPD may respond to lamotrigine when combined with antidepressant medication. The results are sufficiently positive to prompt a larger controlled evaluation of lamotrigine as "add-on" treatment in DPD.

Adolescent↗

PubMed2006

Work of breathing in anesthetized infants increases when a breathing system filter is used.

BACKGROUND: There are concerns that the inclusion of a pediatric heat and moisture exchange filter (HMEF) is in a breathing system may cause an unacceptable increase in the work of breathing. This study is the first study to objectively measure the increase in work of breathing in the infant population when an HMEF is added to the pediatric breathing circuit. METHODS: Ten patients weighing 3-8 kg were studied in a randomized crossover trial. Work of breathing was analyzed using the integral of pressure-volume loops. RESULTS: The median increase in the work of breathing associated with the addition of an HMEF was 279 mJ x min(-1) (95% CI, 165-903 mJ x min(-1)). This equates with a percentage increase of 43% (95% CI, 25-138%). CONCLUSIONS: Because of the substantial increase in the work of breathing with an HMEF attached to the tracheal tube, consideration should be given to alternative means of humidification and filtration during periods of spontaneous ventilation in small infants.

Anesthesia↗

PubMed2005

Pharmacokinetic studies on Wilfactin, a von Willebrand factor concentrate with a low factor VIII content treated with three virus-inactivation/removal methods.

OBJECTIVE: In order to correct the primary von Willebrand factor (VWF) defect and avoid supra-physiologic plasma levels of factor VIII, a pure VWF concentrate almost devoid of FVIII was developed and used in France since 1989. METHODS: The pharmacokinetic (PK) profile of the most recent version of this concentrate (Wilfactin; LFB, Les Ulis, France), treated with three virus-inactivation/removal methods (solvent/detergent, 35 nm filtration, dry heat treatment), was investigated in 25 patients. Seventeen patients with various types of clinically severe von Willebrand disease (VWD) were included in a crossover, randomized trial carried out in five European centers and comparing Wilfactin with concentrates containing both FVIII and VWF (FVIII/VWF). Eight type 3 VWD patients were included in another trial carried out in six French centers comparing Wilfactin with its previous version (Facteur Willebrand-LFB; LFB) that adopted one virus-inactivation method only. RESULTS: For both the measurements evaluated in this study (VWF antigen, VWF:Ag; and VWF ristocetin co-factor activity, VWF:RCo), Wilfactin had a PK profile similar to that of the FVIII/VWF concentrates and of Facteur Willebrand-LFB. VWF:RCo and VWF:Ag recoveries were 2.1 +/- 0.3 and 1.8 +/- 0.3 per IU kg(-1), respectively, and the half-lives were 12.4 +/- 1.8 and 15.9 +/- 1.5 h. The FVIII synthesis rate was 5.8 +/- 1.0 IU dL(-1) h(-1), with a half-life of 15.8 +/- 2.4 h. CONCLUSION: The PK of VWF and FVIII have not been altered by the three virus-inactivation/removal steps during the manufacturing of Wilfactin.

Adult↗

PubMed1996

Effect of polyaspartic acid on pharmacokinetics of gentamicin after single intravenous dose in the dog.

The effects of poly-L-aspartic acid on the pharmacokinetics of gentamicin were examined by using a randomized crossover trial design with the dog. When analyzed according to a three-compartment open model, poly-L-aspartic acid reduced some first-order rate equation constants (A3, lambda 1, and lambda 3), the deep peripheral compartment exit microconstant (k31), the elimination rate constant (k(el)), and the area under the concentration-time curve from 0 to 480 h (AUC0-480) (0.21-, 0.60-, 0.26-, 0.27-, 0.72-, and 0.76-fold, respectively; P < 0.05) but increased the volume of distribution at steady state (Vss), the volume of distribution calculated by the area method (V(area)), the apparent volume of the peripheral compartment (Vp), and all mean time parameters. These results suggested that poly-L-aspartic acid increased the distribution of gentamicin to or binding within the deep peripheral compartment and that poly-L-aspartic acid may have delayed gentamicin transit through the peripheral tissues. In contrast, poly-L-aspartic acid did not alter pharmacokinetic parameters relevant to the central or shallow peripheral compartments to a clinically significant extent. Although gentamicin's pharmacokinetic parameters of relevance to therapeutic drug monitoring were not directly altered, this study has provided pharmacokinetic evidence that poly-L-aspartic acid alters the peripheral distribution of gentamicin. This pharmacokinetic interaction occurred after a single intravenous dose of each drug. Therefore, this interaction should be investigated further, before polyaspartic acid can be considered for use as a clinical nephroprotectant.

Animals↗