OATP1B1 and OATP1B3 are major hepatic drug transporters whilst OATP1A2 is mainly located in the brain but is also located in liver and several other organs. These transporters affect the distribution and clearance of many endo- and xenobiotics and have been reported to have functional SNPs. We have assessed the substrate specificites of these transporters for a panel of antiretrovirals and investigated the effects of SNPs within these transporters on the pharmacokinetics of lopinavir. SLCO1A2, SLCO1B1 and SLCO1B3 were cloned, verified and used to generate cRNA for use in the Xenopus laevis oocyte transport system. Using the oocyte system, antiretrovirals were tested for their substrate specificities. Plasma samples (n=349) from the Liverpool therapeutic drug monitoring registry were genotyped for SNPs in SLCO1A2, SLCO1B1 and SLCO1B3 and associations between SNPs and lopinavir plasma concentrations were analysed. Antiretroviral protease inhibitors, but not non-nucleoside reverse transcriptase inhibitors are substrates for OATP1A2, OATP1B1 and OATP1B3. Furthermore, ritonavir was not an inhibitor of OATP1B1. The 521T>C polymorphism in SLCO1B1 was significantly associated with higher lopinavir plasma concentrations. No associations were observed with functional variants of SLCO1A2 and SLCO1B3. These data add to our understanding of the factors that contribute to variability in plasma concentrations of protease inhibitors. Further studies are now required to confirm the association of SLCO1B1 521T>C with lopinavir plasma concentrations and to assess the influence of other polymorphisms in the SLCO family.

This novel association between CAR rs2307424 and efavirenz plasma concentrations now requires validation in other cohorts.

We investigated the pharmacokinetics and safety of saquinavir/ritonavir when administered with omeprazole simultaneously and 2 h apart to human immunodeficiency virus (HIV) subjects. Saquinavir/ritonavir 12-h pharmacokinetics was assessed with and without omeprazole 40 mg. Subjects were randomized to group A (saquinavir/ritonavir and omeprazole simultaneously/2 h apart) or group B (saquinavir/ritonavir and omeprazole 2 h apart/simultaneously). Saquinavir/ritonavir pharmacokinetics was assessed on days 1, 8, and 22. Within-subject changes were evaluated by geometric mean ratios and 90% confidence interval (CI). Twelve subjects completed the study. GM (90% CI) for saquinavir area under the curve (AUC)(0-12) (ng h/ml), trough concentration (C(trough)) (ng/ml), and maximum concentration (C(max)) (ng/ml) were 14,698 (13,242-20,636), 433 (368-758), 2,513 (2,243-3,329) without omeprazole; 22,646 (18,536-131,861), 750 (619-1,280), 3,890 (3,223-5,133) with omeprazole simultaneously; and 24,549 (20,884-38,894), 851 (720-1,782), 4,141 (3,554-5,992) with omeprazole 2 h earlier. Simultaneous administration of omeprazole significantly increased saquinavir AUC(0-12), C(trough), and C(max) by 54, 73, and 55%, whereas staggered administration by 67, 97, and 65%. No grade 3/4 toxicity or lab abnormalities were observed. In the presence of omeprazole, saquinavir plasma exposure is significantly increased in HIV-infected subjects whether administered simultaneously or 2 h apart.

The potential cardiovascular benefit of virgin olive oil (VOO) is widely recognized. However, the use of VOO at very high cooking temperatures makes these oils poorly suited for many Asian dishes. The use of tea seed oil (TSO) is increasing in Thailand, with TSO having a higher smoke point than VOO. The current study examines the effects of daily TSO intake in healthy adults. In a randomized, single‐blind crossover design, 12 men consumed for 3 weeks 40 g day−1 of food prepared with either TSO or VOO as a cooking oil. Plasma lipids, thiobarbituric acid reactive substances (TBARS), and oxidant defense enzyme activities are measured before and after each 3‐week intervention period. Gas chromatography analysis of TSO and VOO demonstrates that both oils are equally high in monounsaturated fatty acid. The dietary incorporation of TSO and VOO for three weeks reduces low‐density lipoprotein cholesterol (LDL‐C) concentrations by 15% and 13%, respectively; with total cholesterol (TC) levels lowered by 10% in both groups. No significant changes in TBARS or antioxidant enzyme activity is observed. These results support the concept that Thai TSO can be utilized as a suitable and healthy alternative oil for high‐temperature cooking in many Thai and Asian diets. Practical Applications: Tea seed oil from Camellia oleifera grown in Thailand has been recently reported to favorably lower lipid profiles in hamsters fed a high‐fat diet in a manner similar to feeding refined olive oil or grapeseed oil. A pilot crossover trial is conducted to compare the effects of three weeks of daily intake of either TSO or VOO in healthy human adults. Consumption of both oils produced significant reductions in TC and LDL‐C. Thai TSO leads to favorable lipid profiles and is a reasonable choice for many Thai and Asian food recipes.

Significantly higher plasma exposure of some protease inhibitors (PIs) has been observed in Thai subjects compared to Caucasians. These differences may partially be explained by factors such as body weight and diet. However, pharmacogenetic differences may also contribute. The aim of this study was to investigate, in a Thai population, the frequency of functional polymorphisms in genes known to influence plasma concentrations of antiretroviral drugs.