Biomedical subjects

D Jung

Publications and source records attributed to D Jung.

186 records · Page 11Linked to original sources

PubMedDate not supplied

Disposition of procainamide and N-acetylprocainamide in protein-calorie malnutrition.

The influence of dietary protein deficiency on the disposition of procainamide (PA) and its major metabolite, N-acetylprocainamide (NAPA) was investigated in male Sprague-Dawley rats fed for 4 weeks on a 23 (control) or a 5% (low) protein diet ad libitum. Procainamide and N-acetylprocainamide in plasma and urine were determined by a sensitive and specific HPLC assay using a cation-exchange column. After an iv dose of 50 mg/kg procainamide hydrochloride, the average mean residence time (MRT) was approximately 82% higher, while the total plasma clearance (CI) per kg of body weight and terminal elimination rate constant (k) were significantly decreased by 46 and 49%, respectively, in the protein-deficient animals. No significant differences were found in the two groups of animals with respect to the apparent steady state volume of distribution (Vss). Although the percentage of PA recovered unchanged in the urine over 48 hr was not significantly different between control and protein-deficient animals, rats on a low protein diet excreted a smaller percentage of the administered PA dose (mean +/- SE, 19.0 +/- 4.0 vs. 30.8 +/- 1.4%) as NAPA. In addition to the apparent decrease in metabolic clearance (CIm) to NAPA (6.8 +/- 1.4 vs. 19.9 +/- 2.3 ml/min/kg) in the protein-deficient rats, there was a 55% decrease in the renal clearance of PA. There appeared to be no significant difference in the disposition characteristics of NAPA (i.e. MRT, Vss, CI, and k) between the two groups of animals after a 25 mg/kg dose of N-acetylprocainamide hydrochloride.(ABSTRACT TRUNCATED AT 250 WORDS)

Acecainide↗

PubMedDate not supplied

Influence of nutritional status on the pharmacokinetics and pharmacodynamics of pentobarbital.

The influence of dietary protein deficiency on the pharmacokinetics and pharmacodynamics of pentobarbital was investigated in male Sprague-Dawley rats fed for 4 weeks on a 23% (control) or 5% (low) protein diet ad libitum. Following a single iv dose of 40 mg/kg sodium pentobarbital, the average mean residence time (MRT) was prolonged by 144% (2.3 +/- 0.2 to 5.6 +/- 1.5 hr, mean +/- SD) in the protein-deficient rats, whereas the mean total body clearance (CL) per kilogram of body weight decreased from 0.56 +/- 0.09 to 0.22 +/- 0.06 liter/hr/kg. As a result, the terminal disposition rate constant was decreased by approximately 60% (0.398 +/- 0.037 to 0.178 +/- 0.050 hr-1 when compared to rats on a normal protein diet. No significant differences were found in the two groups of rats with respect to the apparent steady state volume of distribution (Vss). In order to investigate the effect of nutritional status on the concentration-pharmacologic activity relationship, pentobarbital was infused iv at a constant rate of 0.55 mg/min until the animals lost their righting reflex (16 +/- 3 min and 8 +/- 1 min in control and protein-deficient animals, respectively). The total dose and concentration of pentobarbital in plasma were not significantly different between the two groups of animals. However, the concentrations of pentobarbital in plasma water (unbound) and brain were appreciably higher in the rats on a low protein diet. Thus, a diet low in protein appears to be associated with a decreased sensitivity of the central nervous system to the depressant effect of pentobarbital.

Animals↗

PubMedDate not supplied

Dose-dependent pharmacokinetics of ibuprofen in the rat.

The linearity of the pharmacokinetics of ibuprofen was examined in male Sprague-Dawley rats given iv bolus doses of 10, 20, and 50 mg/kg ibuprofen. Plasma and urine concentrations of ibuprofen and its two major metabolites, OH-ibuprofen and COOH-ibuprofen, were determined by HPLC and the binding of ibuprofen to plasma proteins was measured by an ultrafiltration technique. The systemic plasma clearance (CLtot) of ibuprofen was dose-dependent and decreased from 0.29 to 0.14 liter/hr/kg primarily as a result of a 65% decrease in the partial metabolic clearance to OH-ibuprofen while the average mean residence time (MRTtot) increased approximately 35% over the 10-50 mg/kg dosage range. Since there were no dose-dependent changes in the apparent steady state volume of distribution (Vss,tot), the mean harmonic half-life increased from 1.7-2.8 hr over the dosage range studied. The binding of ibuprofen to plasma proteins was relatively independent of concentration up to 90 mg/liter (mean free fraction approximately 5.5%), but became markedly concentration-dependent thereafter (free fraction up to 25.4% at 411 mg/liter). The mean recovery of total ibuprofen in the urine over 24 hours at 10 mg/kg was 62.1% and decreased by 24% and 40% at 50 and 20 mg/kg, respectively. This dose-dependent decrease in the percentage excreted in the urine was primarily due to a reduction in the recovery of OH-ibuprofen slightly offset by a small, but significant, increase in the urinary excretion of COOH-ibuprofen between 10 and 50 mg/kg. The apparent pharmacokinetic parameters based on free, unbound concentrations of ibuprofen were also dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Absorption characteristics of three phenytoin sodium products after administration of oral loading doses.

The absorption characteristics of three phenytoin sodium products given orally as loading doses in five healthy men were studied. Extended phenytoin sodium capsules, prompt phenytoin sodium capsules, and phenytoin sodium injection were administered in a randomized, crossover trial as single 18-mg/kg doses and as divided doses of 6 mg/kg every three hours for three doses. Each dose was given with 200 ml of water, and a two-week washout period followed each treatment. The maximum plasma concentration (Cmax), time to reach maximum plasma concentration, time to reach the lower end (10 mg/liter) of the therapeutic range, time to reach a plasma concentration greater than 15 mg/liter, and time within the therapeutic range were determined for each loading-dose regimen. Prompt phenytoin sodium capsules (prompt PHT) given in divided doses produced a mean Cmax of 22.0 mg/liter, which was significantly higher than that observed with any of the other loading-dose regimens. In addition, all subjects receiving prompt PHT in divided doses had plasma phenytoin concentrations of 10 mg/liter within six hours; only this treatment produced plasma concentrations greater than 15 mg/liter at nine hours in all subjects. Plasma concentrations remained within the therapeutic range (10-20 mg/liter) for 81 and 78% of the first 24-hour period for prompt PHT in divided and single doses, respectively. Adverse effects were minimal in all regimens. The prompt-release phenytoin sodium capsules used in this study may provide an alternative means for rapidly achieving therapeutic phenytoin concentrations in situations where i.v. administration is not indicated or practical.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMedDate not supplied

Steady-state pharmacokinetics of enteric-coated naproxen tablets compared with standard naproxen tablets.

In this open-label, randomized, cross-over study, 24 healthy volunteers (12 men and 12 women) received either enteric-coated (EC) naproxen tablets 500 mg twice daily or standard naproxen tablets 500 mg twice daily for 7 days. In each of the two study periods, blood sampling began on day 8, after one last dose of the study drug was administered, to determine and compare steady-state pharmacokinetics for each of the two naproxen formulations. The plasma half-life of naproxen averaged 16.3 and 16.9 hours following EC naproxen and standard naproxen treatments, respectively. Mean time to maximum plasma concentration (Tmax) was greater for EC naproxen than for standard naproxen (4.0 vs 1.9 hours), while the maximum observed plasma concentration (Cmax) was slightly, but not significantly, smaller (94.9 vs 97.4 micrograms/mL, respectively). The mean values for average plasma concentration (Cave) and minimum plasma concentration for EC naproxen were 70.4 and 60.6 micrograms/mL, respectively, compared with 63.9 and 44.1 micrograms/mL for standard naproxen. The mean plasma fluctuation about the mean was greater for standard naproxen than for EC naproxen (85.3% vs 49.3%), while the mean area under the plasma concentration-time curve (AUC) was smaller for standard naproxen (766.8 vs 845.0 micrograms x h/mL). At steady state, EC naproxen was similar to standard naproxen tablets with respect to Cmax, Cave, Cmax:Cave, 0- to 12-hour AUC, and half-life but differed in Tmax. In addition, fluctuations about Cave in plasma levels were considerably lower with EC naproxen than with standard naproxen.

Administration, Oral↗

PubMedDate not supplied

Pharmacokinetics of mycophenolate mofetil and intravenous ganciclovir alone and in combination in renal transplant recipients.

STUDY OBJECTIVES: To evaluate the pharmacokinetics of mycophenolic acid and its glucuronide metabolite alone and in the presence of ganciclovir, and to determine the pharmacokinetics of ganciclovir alone and in combination with mycophenolate mofetil. DESIGN: Randomized, open-label, three-way crossover study. PATIENTS: Twelve kidney transplant recipients. INTERVENTIONS: Mycophenolate mofetil 1500 mg orally and ganciclovir 5 mg/kg intravenously were each given alone and in combination with at least a 1-week washout period between treatment arms. MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained to measure mycophenolic acid and ganciclovir by high-performance liquid chromatography. Mean (+/-SD) oral plasma clearance for mycophenolic acid alone and with ganciclovir was 3.11 +/- 0.72 and 3.19 +/- 0.72 ml/min/kg (p = 0.64). The overall disposition of the major metabolite, MPA-glucuronide, was unchanged, with approximately 70% of the administered dose eliminated as the glucuronide conjugate for both arms of the study. Mean genciclovir serum clearance was 1.80 +/- 0.58 ml/min/kg for ganciclovir and 1.70 +/- 0.55 ml/min/kg for ganciclovir plus mycophenolate mofetil (p = 0.11; 10 patients). Renal clearance of ganciclovir was decreased when the drugs were administered in combination, 1.43 +/- 0.54 (ganciclovir) and 1.26 +/- 0.44 (both drugs) ml/min/kg (p = 0.02; 10 patients). CONCLUSION: The single-dose pharmacokinetics of mycophenolic acid and its glucuronide metabolite were unchanged by the addition of ganciclovir. Total serum clearance of ganciclovir was unchanged by the addition of mycophenolate mofetil, however, renal clearance was slightly decreased.

Adult↗