Population pharmacokinetics of intravenous and intramuscular streptomycin in patients with tuberculosis

Study Objectives. To determine population pharmacokinetic parameters of streptomycin after administration of multiple intramuscular and intravenous doses. Design. Prospective, unblinded clinical study. Setting. Two medical centers in Denver, Colorado. Patients. Thirty patients with tuberculosis. Intervention. Patients received multiple doses of streptomycin as part of their tuberculosis treatment. They received concurrent drugs based on in vitro susceptibility data. Measurements and Main Results. Serum samples were collected over a 10-hour period and assayed by validated high-performance liquid chromatography Concentration-time data were analyzed using population methods. Streptomycin concentrations increased linearly with increasing intravenous doses. The intramuscular doses did not produce as linear a relationship, presumably because of variability in rates of and, potentially, completeness of absorption. Streptomycin elimination decreased with declining renal function. Higher, intermittent doses were well tolerated and appeared to maximize the peak concentration:minimal inhibitory concentration ratio. Conclusion. Overall, pharmacokinetic parameters of streptomycin were comparable with those previously published for streptomycin and other aminoglycosides. Higher, intermittent doses maximize pharmacodynamic parameter estimates and might have advantages for treatment of tuberculosis.