Population pharmacokinetics of caffeine in healthy male adults using mixed-effects models.

OBJECTIVE: Caffeine has been shown to maintain or improve the performance of individuals, but its pharmacokinetic profile for Asians has not been well characterized. In this study, a population pharmacokinetic model for describing the pharmacokinetics of caffeine in Singapore males was developed. The data were also analysed using non-compartmental models. METHODS: Data gathered from 59 male volunteers, who each ingested a single caffeine capsule in two clinical trials (3 or 5 mg/kg), were analysed via non-linear mixed-effects modelling. The participants' covariates, including age, body weight, and regularity of caffeinated-beverage consumption or smoking, were analysed in a stepwise fashion to identify their potential influence on caffeine pharmacokinetics. The final pharmacostatistical model was then subjected to stochastic simulation to predict the plasma concentrations of caffeine after oral (204, 340 and 476 mg) dosing regimens (repeated dosing every 6, 8 or 12 h) over a hypothetical 3-day period. RESULTS: The data were best described by a one-compartmental model with first-order absorption and first-order elimination. Smoking status was an influential covariate for clearance: clearance (mL/min) = 110*SMOKE + 114, where SMOKE was 0 and 1 for the non-smoker and the smoker respectively. Interoccasion variability was smaller compared to interindividual variability in clearance, volume and absorption rate (27% vs. 33%, 10% vs. 15% and 23% vs. 51% respectively). The extrapolated elimination half-lives of caffeine in the non-smokers and the smokers were 4.3 +/- 1.5 and 3.0 +/- 0.7 h respectively. Dosing simulations indicated that dosing regimens of 340 mg (repeated every 8 h) and 476 mg (repeated every 6 h) should achieve population-averaged caffeine concentrations within the reported beneficial range (4.5-9 microg/mL) in the non-smokers and the smokers respectively over 72 h. CONCLUSION: The population pharmacokinetic model satisfactorily described the disposition and variability of caffeine in the data. Mixed-effects modelling showed that the dose of caffeine depended on cigarette smoking status.

Review of dengue fever cases in Hong Kong during 1998 to 2005.

OBJECTIVE: To describe the epidemiology, clinical and laboratory findings, and outcomes of patients presenting locally with dengue. DESIGN: Retrospective review of case records. SETTING: Public hospitals, Hong Kong. PATIENTS: Medical records of all laboratory-confirmed dengue patients admitted to public hospitals during 1998 to 2005 were reviewed retrospectively. RESULTS: A total of 126 cases were identified, 123 (98%) being dengue fever and three (2%) dengue haemorrhagic fever. One patient who had blood transfusion-acquired dengue fever was highlighted. A total of 116 (92%) cases were 'imported', while 10 (8%) were local. Among the 56 dengue cases confirmed by reverse transcription-polymerase chain reaction, dengue virus type 1 was the most common accounting for 48% of them, followed by type 2, type 3, and type 4 responsible for 23%, 16%, and 13%, respectively. Only type 1 and type 2 were present in locally acquired infections. The median age of the patients was 38 years and the mean duration of hospitalisation was 6 days. There was no mortality, and nearly all patients (98%) presented with fever. Other symptoms at presentation included: myalgia (83%), headache (65%), fatigue (59%), and skin rash (60%). More than one third of patients had gastro-intestinal and upper respiratory complaints. Maculopapular skin rash was the most common physical finding. Thrombocytopenia, neutropenia, and lymphopenia were present in 86%, 78%, and 69% of the patients, respectively. In only 29% of the patients was dengue fever included in the initial differential diagnosis. The demographic, clinical, and laboratory findings as well as outcomes did not differ significantly among the four dengue serotypes, but the lowest lymphocyte counts of type 3 was lower than the other serotypes (P=0.004). CONCLUSION: When physicians encounter patients with a relevant travel history, presenting with fever and skin rash, and having compatible haematological findings, dengue fever should be included in the differential diagnosis.

Influence of catechins on bystander responses in CHO cells induced by alpha-particle irradiation.

In this work, we studied alpha-particle induced and medium-mediated bystander effects in Chinese hamster ovary (CHO) cells through micronucleus (MN) assay. We showed that signal transduction from irradiated cells to bystander cells occur within a short time after irradiation. We then studied the effects of ROS (reactive oxygen species)-scavenging catechins in the medium before irradiation. We observed decreases in the percentage of bystander cells with MN formation and thus proved the protection effect of catechins on bystander cells from radiation.

Influence of Magnolol on the bystander effect induced by alpha-particle irradiation.

In this work, the influence of Magnolol on the bystander effect in alpha-particle irradiated Chinese hamster ovary (CHO) cells was examined. The bystander effect was studied through medium transfer experiments. Cytokinesis-block micronucleus (CBMN) assay was performed to quantify the chromosome damage induced by alpha-particle irradiation. Our results showed that the alpha-particle induced micronuclei (MN) frequencies were suppressed with the presence of Magnolol.