Theophylline pharmacokinetics in black Zimbabwean males

Theophylline pharmacokinetics were studied in 16 black Zimbabwean volunteers aged 20-41 years. Following a single intravenous dose of 5 mg/kg, four serum levels were collected over 24 h. Data were analyzed using a one-compartment open model. The correlation coefficient was 0.995 +/- 0.004. The mean extrapolated peak level was 8.5 +/- 0.9 mg/L. The mean half-life and volume of distribution were 10.1 +/- 3.1 h and 0.55 +/- 0.7 L/kg, respectively. The mean clearance was 0.62 +/- 0.17 ml/kg/min. The mean weight was 7 kg less than the calculated ideal body weight. These data suggest a larger volume of distribution and longer half-life than in other reported populations. The clearance is on the low end of previously reported values. We postulate that the primary cause of the large volume is the decreased body fat and consequent increase in body water per kilogram. The slightly decreased clearance may have been partially due to the high carbohydrate, low protein diet of our subjects. The long half-life is simply a reflection of a large volume and a moderately low clearance. We suggest that standard per kilogram maintenance doses can be employed in this population. A larger loading dose of 8 mg/kg aminophylline is recommended. Finally, the lack of sustained release theophylline in Zimbabwe may not be a problem, given the longer half lives observed in this study.