Pharmacokinetics of sirolimus in Thai healthy volunteers.

Sirolimus, a novel immunosuppressive drug, has been used in kidney transplant recipients to minimize calcineurine inhibitor (CNI) and steroid toxicities. Likewise CNI, Sirolimus's pharmacokinetics have both inter and intra-individual pharmacokinetic variations. Due to ethnic differences, the recommended oral loading dose of 6 mg and oral maintenance dose of 2 mg per day for Caucasian patients and oral loading dose of 10 mg and oral maintenance dose of 5 mg per day for African-American patients may not be appropriate for Asian recipients. We, therefore conducted the pharmacokinetic study of sirolimus in Thai population, aimed to delineate the appropriate sirolimus dose for further clinical use. The study was performed in 12 healthy Thai volunteers. After an over night fasting, a single oral dose of 6 mg sirolimus was given. The complete pharmacokinetic study was done by UVhigh performance liquid chromatography (HPLC-UV) to measure the whole blood sirolimus level at 0.5 hour after the dose (C0.5) and then C1, C1.5, C2, C2.5, C3, C4, C6, C8, C12, and C24 hours. A complete area under the concentration time curve from 0-24 hours (AUC(0-24 hr)) was calculated by using the trapezoidal rule. The mean (+/- SD) time to maximal concentration (Tmax) was 1.45 +/- 0.5 hr (range 1-3 hrs). The maximal (Cm) and minimal plasma concentration (Ctroug) for sirolimus were 25.3 +/- 6.1 ng/ml (range 18.10 - 40 ng/ml) and 4.47 +/- 0.57 ng/ml (range 2.90 - 7.20) ng/ml respectively. The AUC(0-24 hr) were 187.9 +/- 48.2 ng * hr/ml (range 151.3 - 294.8 ng * hr/ml). Sirolimus level at 4 hr post-dose had the best of correlation with AUC(0-24 hr) (Pearson correlation = 0.76, p < 0.007). One volunteer had a very high sirolimus level. This subject's pharmacokinetic data showed AUC(0-24 hr) of 256 ng * hr/ml and Cmax of 40 ng/ml. In conclusion, the oral loading dose of 6 mg of sirolimus in Thai volunteers did not achieve the recommended therapeutic level (5-10 ng/ml) in most subjects. There are differences in pharmacokinetics of sirolimus between Thais and Caucasians.

Prediction of UGIB event in NSAID users: a model development.

The purpose of this study was to create a predicting tool for UGIB event in NSAID users. The patients of this case-control study were NSAID users who had received NSAIDs for at least 3 days and were gastroscoped The patients with a history of gastrointestinal varices, gastrointestinal cancer, chronic renal failure, coagulopathy, or Mallory-Weiss tear were excluded. The data was collected between July 2001 and January 2002 by patient interviewing and medical record reviewing. One hundred and fifty four NSAID users were identified (89 in the UGIB group, 65 in the non-bleeding group). Most patients were elderly (mean age +/- SD: 60.9 +/- 12.6 years). Age and the number of current NSAID users were significantly higher in UGIB patients than in non-bleeding patients (p < 0.05 and p < 0.01, respectively). The number of antiulceration drug users in non-bleeding patients was higher than in UGIB patients (p < 0. 01). An equation for prediction of UGIB probability in NSAID users was generated by using enter logistic regression. The best model of predicting the risk of UGIB event in NSAID users was logit (UGIB) = 0.33 + 2.09 Multiple NSAID use + 1.43 H. pylori infection + 0.34 Current NSAID use + 0.12 (Age x Sex) - 8.53 Sex - 2.41 Antiulceration drugs - 0. 000048 Age. The model had 80.2% of the overall rate of correct classification. The positive and negative predictive values were 80.8% and 78.9% respectively. The probability of UGIB = e((logit(UGIB)) /1 + e(logit(UGlB)). If the value of the probability of UGIB is more than 0. 5, the patient has a high risk of UGIB. Multiple NSAID use is the strongest factor that affects the probability of UGIB in NSAID users. H. pylori infection is another strong risk factor of NSAID-related UGIB. Antiulceration drug usage reduced the risk of UGIB in this group of patients. The developed model can be used as a guide for pharmacotherapeutic planning in clinical practices.

Prevalence of lipodystrophy in Thai-HIV infected patients.

To determine the prevalence and clinical characteristics of lipodystrophy in HIV-infected Thai patients, a cross-sectional study was performed on 278 HIV-infected patients at Bamrasnaradura Infectious Disease Institute. Laboratory data related to lipid and glucose metabolism were obtained from both patients who self reported fat maldistribution or diagnosed by a physician. The history of antiretroviral treatment and HIV infection were recorded. Prevalence of lipodystrophy found in the present study was 17%. Lipodystrophy was reported mostly on the face, buttock, legs, arms, and abdomen respectively. Two-thirds of these patients had mixed syndromes of fat accumulation and fat wasting and the others had only fat wasting. Ninety-three percent of lipodystrophic patients had at least 1 abnormality in either lipid or glucose metabolism. Eighty-eight percent had dyslipidemia, 21% had impaired glucose tolerance, 30% had insulin resistance and 27% had diabetes mellitus. Lipodystrophic patients have a high rate of lipid and glucose metabolism abnormalities which are the major risk factors for cardiovascular events.