151. Systematically individualizing tobramycin dosage regimens
- Author
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Robert J. Cipolle, Richard G. Strate, Darwin E. Zaske, and Randall D. Seifert
- Subjects
Adult ,Male ,medicine.medical_specialty ,Aging ,Time Factors ,Adolescent ,Microgram ,Urology ,Renal function ,Nephrotoxicity ,Ototoxicity ,Pharmacokinetics ,Tobramycin ,Medicine ,Humans ,Pharmacology (medical) ,In patient ,Child ,Aged ,Pharmacology ,business.industry ,Infant ,Liter ,Bacterial Infections ,Middle Aged ,medicine.disease ,Anti-Bacterial Agents ,Kinetics ,Child, Preschool ,Female ,business ,medicine.drug - Abstract
Tobramycin dosage regimens were individually calculated from serum concentration-time data in 64 patients. Tobramycin pharmacokinetic parameters and dosage requirements demonstrated wide interpatient variation. The tobramycin half-life varied from 0.5 to 8.6 hours in patients with normal serum creatinines. The mean (+/- S.D.) distribution volume was 0.22 (+/- 0.09) liter/kg for all patients. Dosage requirements were higher for the younger patients, however, considerable variability existed within age groups. In patients with normal serum creatinines, an 8-hour dosing interval was optimal in only 17 of the 46 patients. A multiple regression model using age, weight, and creatinine clearance could explain only 44.2% of the variance in tobramycin clearance. Measured steady-state peak and trough concentrations compared favorably with desired peak and trough concentrations. The mean (+/- S.D.) desired peak was 7.2 (+/- 1.8) microgram/ml, and the mean (+/- S.D.) measured peak was 7.1 (+/- 2.0) microgram/ml. The mean (+/- S.D.) desired trough was 1.1 (+/- 0.9) microgram/ml, and the mean (+/- S.D.) measured trough was 1.3 (+/- 0.8) microgram/ml. Many patients required dosage regimens exceeding those commonly recommended; however, no cases of ototoxicity or nephrotoxicity were encountered. This model proved successful in calculating dosage regimens of tobramycin to obtain optimal serum concentrations.
- Published
- 1980