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J R Koup

Publications and source records attributed to J R Koup.

94 records · Page 6Linked to original sources
PubMedDate not supplied

Pharmacokinetics of high-dose azlocillin sodium in patients with cystic fibrosis.

The pharmacokinetics of high-dose azlocillin sodium was studied in 18 patients with cystic fibrosis. Nine male and nine female patients with a mean age of 14.7 years (range 3 to 29 years) participated in the study. They received azlocillin 450 mg/kg/day (as the sodium salt) in six divided doses. During a steady-state dosing interval, a dose of azlocillin was coadministered with a 10-mg/kg dose of iothalamate sodium as a 30-minute infusion. Serum concentrations of azlocillin and iothalamate were determined by high-pressure liquid chromatography assay. The data were analyzed using model-independent methods. The mean elimination rate constant for azlocillin was 0.64 +/- 0.22 hr-1 and the mean serum half-life was 1.22 +/- 0.39 hr. Total clearance of azlocillin, calculated by noncompartmental analysis, was 77.2 +/- 26.4 mL/min/sq m. Glomerular filtration rate, as estimated by measuring iothalamate clearance, was 79.6 +/- 21.9 mL/min/sq m. The total clearance of azlocillin correlated with iothalamate clearance. Patients with cystic fibrosis appear to eliminate azlocillin more rapidly than healthy individuals. This rapid elimination warrants the use of high doses to maintain high serum concentrations.

Adolescent↗
PubMedDate not supplied

Nonlinear regression program to individualize oral theophylline dosage.

Theophylline pharmacokinetic values were estimated by two similar computer-assisted methods, and the predictive ability of these methods was evaluated. In each of two study phases, baseline serum theophylline concentrations were obtained in 20 adults receiving oral theophylline for chronic obstructive pulmonary disease; the subjects received no theophylline for 48 hours before start of each phase. In phase 1 all patients received theophylline 400 mg followed by 300 mg every six hours for three doses, and serum theophylline concentrations were measured at 0-6 hours and at 24 hours. In phase 2 patients received individualized theophylline doses calculated from phase 1 data. Predictive method 1 used measured serum theophylline concentrations at 2, 6, and 24 hours to estimate pharmacokinetic values, and method 2 used concentrations at 6 and 24 hours. The computer-predicted values were used to calculate 24-hour serum theophylline concentrations for individualized regimens in phase 2; these were compared with the measured concentration. Pharmacokinetic values predicted by both methods were compared with values based on data obtained after the loading dose in phase 1. Both methods were unbiased when predicting clearance, half-life, and volume of distribution. Estimates of half-life and volume of distribution were significantly more precise with method 1. Both methods underpredicted serum theophylline concentration at 24 hours. The greater number of serum concentrations in method 1 allowed more precise prediction of t1/2 and V; in instances where precision is not critical, method 2 is an acceptable alternative.

Adult↗