Population pharmacokinetics of intravenous and intramuscular streptomycin in patients with tuberculosis.
OBJECTIVE
To determine population pharmacokinetic parameters of streptomycin after administration of multiple intramuscular and intravenous doses.


METHODS
Prospective, unblinded clinical study.


METHODS
Two medical centers in Denver, Colorado.


METHODS
Thirty patients with tuberculosis.


METHODS
Patients received multiple doses of streptomycin as part of their tuberculosis treatment. They received concurrent drugs based on in vitro susceptibility data.


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.


CONCLUSIONS
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.
Zhu
M
M
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Burman
W J
WJ
Jaresko
G S
GS
Berning
S E
SE
Jelliffe
R W
RW
Peloquin
C A
CA
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011153:Population; D011446:Prospective Studies; D011786:Quality Control; D013307:Streptomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014376:Tuberculosis / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D013307:Streptomycin