Pharmacokinetics of diltiazem and its major metabolite, deacetyidiltiazem after oral administration of diltiazem in mild and medium folate-induced renal failure rabbits.

The pharmacokinetic changes of diltiazem (DTZ) and its main metabolite, deacetyldiltiazem (DAD) were studied after oral administration of DTZ to normal rabbits and mild and medium folate-induced renal failure rabbits. DTZ 10 mg/kg was given to the rabbits either orally (n=6). Plasma concentrations of DTZ and DAD were determined by a high performance liquid chromatography assay. The area under the plasma concentration-time curves (AUC) and maximum plasma concentration (Cmax) of DTZ were significantly increased in mild and medium folate-induced renal failure rabbits. The metabolite ratio of the DTZ to DAD were significantly decreased in mild and medium folate-induced renal failure rabbits. The volume of distribution (Vd) and total body clearance (CLt) of DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits. The elimination rate constant (beta) of DTZ was significantly decreased in folate-induced renal failure rabbits, but that of DAD was significantly increased. These findings suggest that the hepatic metabolism of DTZ was inhibited and the Vd, CLt and beta of DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits.

Circadian changes in the pharmacokinetics of triamcinolone acetonide in rabbits.

Circadian changes in the pharmacokinetics of triamcinolone acetonide were investigated in rabbits after a single intravenous administration of the drug, 1.0 mg/kg, at 08:00 and 20:00. At 20:00 hrs, the area under the plasma concentration-time curve from time zero to time infinity was significantly greater (46% increase), and this could be due to significantly slower total body clearance (31% decrease) than that at 08:00. The terminal half-life was significantly longer (82%) at 20:00. However, the apparent volume of distribution at steady state and total amount of unchanged drug excreted in 12 hr urine were not significantly different between two groups of rabbits.

Stability of ondansetron and fluconazole in 5% dextrose injection and normal saline during Y-site administration.

The stability of ondansetron and fluconazole in 5% dextrose injection and normal saline during simulated Y-site injection at room temperature was studied. Ondansetron 0.03, 0.1 and 0.3 mg/ml were admixed 1ratio1 with fluconazole 2 mg/ml. The solutions were stored at room temperature and samples were retrieved at time 0, 1, 2, 4 and 12 hr for immediate assay. At the time of the assay and before any dilution, each sample was visually inspected for clarity, color, precipitation, and the pH was determined. Drug concentrations were measured by a stability-indicating high performance liquid chromatograph. Ondansetron 0.03, 0.1 and 0.3 mg/ml were stable when mixed with concentration of fluconazole 2 mg/ml. There were no change in clarity and color and no precipitates in any admixture for 12 hr of inspection. The pH measurements did not have a particular trend in any direction over time.

Piperacillin-tazobactam pharmacokinetics in patients with intraabdominal infections.

STUDY OBJECTIVE: To determine the appropriate compartmental and noncompartmental pharmacokinetic parameters for intravenous piperacillin and tazobactam. DESIGN: Sequential selection of patients entered into a randomized, open-label clinical efficacy trial. SETTING: Los Angeles County-University of Southern California Medical Center. PARTICIPANTS: Sequential sample of 18 patients admitted for intraabdominal infections and consented into a comparative antibiotic trial. INTERVENTIONS: Patients received piperacillin 4 g plus tazobactam 500 mg by intravenous intermittent infusion every 8 hours. MEASUREMENTS AND MAIN RESULTS: The estimated noncompartmental pharmacokinetic parameters (mean +/- SD) for piperacillin and tazobactam, respectively, were as follows: maximum concentration in plasma 218.7 +/- 48.9 micrograms/ml and 27.8 +/- 9.1 micrograms/ml; half-life 1.07 +/- 0.22 hours and 1.00 +/- 0.27 hours; elimination rate constant 0.67 +/- 0.13 hr-1 and 0.73 +/- 0.18 hr-1; area under the concentration-time curve from zero hour to infinity 288.5 +/- 71.25 mg.hr/L and 36.3 +/- 9.55 mg.hr/L; total plasma clearance 14.75 +/- 3.93 L/hour and 14.78 +/- 4.39 L/hour; renal clearance 5.69 +/- 1.94 L/hour and 7.85 +/- 3.37 L/hour; volume of distribution at steady state 21.00 +/- 4.18 L and 22.47 +/- 8.27 L; and mean residence time 1.72 +/- 0.29 hours and 1.79 +/- 0.35 hours. CONCLUSION: Our findings were similar to those in other surgical patient models. The two-compartmental model best described piperacillin and tazobactam disposition in our patients. Bayesian analyses of the two-compartment models of piperacillin and tazobactam were able to predict trough, peak, and 2-hour postadministration levels without bias.

Comparison of aminoglycoside pharmacokinetics in Asian, Hispanic, and Caucasian patients by using population pharmacokinetic methods.

A population pharmacokinetic model for aminoglycosides was developed from 24 Hispanic, 16 Asian, and 22 Caucasian patients. A nonparametric expectation maximization algorithm for population modeling was used. With this one-compartment model, the parameters were the slope of the apparent volume of distribution versus weight (VS) and the slope of the elimination rate constant versus the creatinine clearance rate (KS). The mean VS (+/- standard deviation) was not different at 0.264 (+/- 0.05), 0.248 (+/- 0.055), and 0.260 (+/- 0.080) liter/kg of body weight for Asian, Hispanic, and Caucasian populations, respectively (P > 0.10). The KS means +/- standard deviations were 0.00424 +/- 0.00129, 0.00404 +/- 0.00160 and 0.00394 0.00103 [h(ml/min/1.73 m2)]-1 +/- for Hispanic, Asian, and Caucasian populations, respectively. Again, there was no statistical difference among the groups (P > 0.10). In conclusion, there are no differences in aminoglycoside pharmacokinetics among Asian, Hispanic, and Caucasian patients.

Stability of piperacillin sodium-tazobactam sodium and ranitidine hydrochloride in 0.9% sodium chloride injection during simulated Y-site administration.

The stability of piperacillin sodium plus tazobactam sodium and ranitidine hydrochloride in 0.9% sodium chloride injection during simulated Y-site administration was studied. Triplicate test solutions of piperacillin 40 mg/mL plus tazobactam 5 mg/mL (as the sodium salts) or piperacillin 80 mg/mL plus tazobactam 10 mg/mL (as the sodium salts) were mixed 1:1 with ranitidine 0.5 and 2.0 mg/mL (as the hydrochloride salt). The solutions were stored at 23 degrees C, and samples were removed at zero, one, two, and four hours for measurement of drug concentration by stability-indicating high-performance liquid chromatography. At the time of sampling and before any dilution, each sample was visually inspected for color and precipitation, and pH was determined. At all sampling times, the concentrations of piperacillin, tazobactam, and ranitidine were > 90% of initial concentrations. There were no substantial changes in pH or color. Tazobactam 5 mg/mL (as the sodium salt) and ranitidine 0.5 and 2 mg/mL (as the hydrochloride salt) in 0.9% sodium chloride injection were stable for up to four hours during simulated Y-site administration. Piperacillin 80 mg/mL plus tazobactam 10 mg/mL (as the sodium salts) and ranitidine 0.5 and 2 mg/mL (as the hydrochloride salt) were stable for up to four hours during simulated Y-site administration.

Stability of paclitaxel with ondansetron hydrochloride or ranitidine hydrochloride during simulated Y-site administration.

The stability of paclitaxel with either ondansetron hydrochloride or ranitidine hydrochloride during simulated Y-site injection at room temperature was studied. Triplicate test solutions of paclitaxel 0.3 and 1.2 mg/mL were admixed 1:1 with ondansetron 0.03 and 0.3 mg/mL (as the hydrochloride salt) or ranitidine 0.5 and 2.0 mg/mL (as the hydrochloride salt). Also, paclitaxel 1.2 mg/mL was admixed 1:1:1 with ondansetron 0.3 mg/mL and ranitidine 2.0 mg/mL. The solutions were stored in glass containers at room temperature, and samples were removed at zero, one, two, and four hours for immediate assay. At the time of the assay and before any dilution, each sample was visually inspected for clarity, color, and precipitation, and the pH was determined. Drug concentrations were measured by stability-indicating high-performance liquid chromatographic procedures. Throughout the study, more than 90% of the initial concentrations of paclitaxel, ondansetron, and ranitidine remained in the solutions. No precipitates, color changes, or haziness was seen. The changes in pH were minor. Paclitaxel in concentrations of 0.3 and 1.2 mg/mL was stable when mixed with either ondansetron (0.03 or 0.3 mg/mL, as the hydrochloride salt) or ranitidine (0.5 or 2.0 mg/mL, as the hydrochloride salt) and stored in glass containers for four hours. Paclitaxel 1.2 mg/mL was also stable when mixed with both ondansetron 0.3 mg/mL and ranitidine 2.0 mg/mL and stored in glass containers for four hours.