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There is a wide interethnic variance in the pharmacokinetic profile of clozapine (CLZ), but the accumulated data are limited to some regional populations. In this study, we investigated the pharmacokinetic profile of CLZ in Korean patients and examined the association between serum CLZ parameters and clinical outcome. We assessed 78 Korean patients with schizophrenia who had been taking CLZ medication for more than 6 months. The patients were classified into three groups (good, moderate, and poor responders) according to their Clinical Global Impressions-Improvement scores. The serum concentrations of CLZ and norclozapine were 610.7±368.4 and 314.5±163.0 ngml (mean±SD), respectively, showing a large interindividual variation that was affected by dose, age, smoking habits, and sex by variable degrees. The pharmacokinetic profiles of Koreans were similar to those observed in Asians but quite different from those in Caucasians. Investigation on clinical responses revealed that the good or moderate responders clinically improved at a relatively low serum CLZ levels, whereas the poor responders showed less improvement despite the higher doses and serum levels. The metabolic ratio of the good responders was 0.65±0.20, higher than the poor responders (P0.033). In this study, we identified a pharmacokinetic profile of CLZ in Korean schizophrenia patients and found a wide interindividual difference affected by various factors.

ABSTRACTStaphylococcus aureus, one of the most frequently isolated pathogens in both hospitals and the community, has been particularly efficient at developing resistance to antimicrobial agents. As methicillin-resistant S. aureus(MRSA) has prevailed and, furthermore, as S. aureuswith reduced susceptibility to vancomycin has emerged, the therapeutic options for the treatment of S. aureusinfections have become limited. To update the current status of antibiotic resistance, clinical S. aureusisolates were collected from eight university-affiliated hospitals from June 1999 to January 2001. Susceptibility tests with 28 antibiotics were performed by the disk diffusion method. Among a total of 682 isolates, the methicillin resistance rate was 64% (439 of 682), and most of the MRSA isolates were resistant to multiple classes of antibiotics. Although a constitutive macrolide-lincosamide-streptogramin B resistance phenotype was common, no isolates were resistant to quinupristin-dalfopristin or linezolid. Rifampin, fusidic acid, trimethoprim-sulfamethoxazole, and arbekacin showed superior in vitro activity compared with the other antibiotics against the MRSA isolates. No isolates showed reduced susceptibility to vancomycin.