Population pharmacokinetics of vancomycin in Japanese adult patients.
Population pharmacokinetic parameters of vancomycin (VCM) in Japanese adult patients infected with methicillin-resistant Staphylococcus aureus (MRSA) were estimated using 1253 items of serum concentration data from 190 patients obtained in routine drug monitoring. The two-compartment linear model was adopted, and VCM clearance (CL) was correlated with the creatinine clearance (CLcr), which was observed or estimated by the Cockcroft-Gault equation. The population pharmacokinetic analysis program NONMEM with first-order conditional estimation method was used. The results showed VCM clearance to be linearly correlated with CLcr (CL [ml/min] = 0.797 x CLcr) when the estimated CLcr was <85 ml/min, but no linear relationship at higher than this level because of the lack of accuracy in the CLcr estimates. The interindividual variability of CL was 38.5%; K12 and K21 were 0.525 hr(-1) and 0.213 hr(-1), respectively. The distribution volume at steady state (V[SS]) was 60.71, with no significant dependence on the actual body weight. The interindividual variability of Vss was 25.4%. The calculated half-life (t1/2,beta) in a typical patient with CLcr of 85 ml/minute was 12.8 hours. Residual variability was 23.7%. These results were compared to those of healthy volunteers, and guidelines for dosage adjustment in VCM therapy are discussed.
Yasuhara
M
M
Department of Pharmacy, Tokyo Medical and Dental University Hospital, Japan.
Iga
T
T
Zenda
H
H
Okumura
K
K
Oguma
T
T
Yano
Y
Y
Hori
R
R
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044466:Asian People; D001499:Bayes Theorem; D003404:Creatinine / Q000097:blood; D003710:Demography; D016903:Drug Monitoring; D005260:Female; D006207:Half-Life; D006801:Humans; D007564:Japan / Q000453:epidemiology; D016018:Least-Squares Analysis; D008297:Male; D016106:Methicillin Resistance; D008875:Middle Aged; D008954:Models, Biological; D015233:Models, Statistical; D012016:Reference Values; D015203:Reproducibility of Results; D013203:Staphylococcal Infections / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D014640:Vancomycin; D003404:Creatinine