Effect of morphine or phenobarbital on teicoplanin elimination pharmacokinetics.
Elimination kinetics following a single dose of teicoplanin in rats pre-treated with morphine sulphate (MS), phenobarbital sodium (Pb), and normal saline (NS) were determined. A microbioassay was used to measure teicoplanin levels. A significant increase in the total clearance of teicoplanin was found in rats pre-treated with MS as compared to controls (P < 0.048). Wide variability was observed in the renal and non-renal clearances of teicoplanin. The mean renal clearance for rats pre-treated with MS, Pb and NS was 0.61 +/- 0.07.mL/min/kg, 0.60 +/- 0.13 mL/min/kg, and 0.46 +/- 0.02 mL/min/kg, respectively; the mean non-renal clearance was 0.33 +/- 0.18 mL/min/kg, 0.17 +/- 0.15 mL/min/kg, and 0.08 +/- 0.03 mL/min/kg, respectively. The differences among the groups for renal and non-renal clearance were not statistically significant. The mean apparent volume of distribution of teicoplanin at steady state was significantly lower in the Pb-pre-treated rats as compared to controls (P < 0.043). The mean half-life for MS-, Pb-, and NS pre-treated groups was 8.1 +/- 3.1 h, 5.9 +/- 3.3 h, and 34.6 +/- 20.7 h, respectively. The differences in mean half-life among the groups achieved statistical significance (P < 0.016). The increase in the total clearance of teicoplanin can best be explained by an increase in both renal elimination and hepatic metabolic pathways.
Fan-Havard
P
P
Rutgers College of Pharmacy, Piscataway, NJ.
Koshy
Z
Z
Bais
R M
RM
Smith
C
C
Eng
R H
RH
D000818:Animals; D004697:Endocarditis, Bacterial / Q000382:microbiology; D006207:Half-Life; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015610:Serum Bactericidal Test; D017334:Teicoplanin / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D017334:Teicoplanin; D009020:Morphine; D010634:Phenobarbital