AIMThe organic cation transporter 1 (OCT1) plays a key role in the cellular transport of metformin and its subsequent glucose-lowering effect. A recent non-clinical study reported that metformin uptake into hepatocytes is regulated via OCT1, and that uptake was strongly inhibited by verapamil. Therefore, we investigated the effects of verapamil co-administration on the pharmacokinetics and pharmacodynamics of metformin in humans. METHODSWe evaluated the pharmacokinetics and the anti-hyperglycaemic effects of metformin using an oral glucose tolerance test (OGTT) in 12 healthy participants, before (day 1) and after metformin treatment (day 2), and again on days 15 and 16 after co-administration with verapamil. RESULTSVerapamil inhibited the ability of metformin to reduce maximum blood glucose concentrations (ΔGmax) by 62.5% (P = 0.008) and decreased the area under the glucose concentration-time curve (ΔAUCgluc) by 238% (P = 0.015). However, verapamil did not significantly alter the Cmax and the AUC of metformin, nor its renal clearance. CONCLUSIONSOur results suggest that verapamil remarkably decreases the glucose-lowering effect of metformin, possibly by acting as a competitive inhibitor of OCT1.
Please cite this paper as: Kim et al. (2012) Is abdominal obesity associated with the 2009 influenza A (H1N1) pandemic in Korean school‐aged children? Influenza and Other Respiratory Viruses 6(5), 313–317. Objective Given their medical vulnerabilities, we investigated the epidemiological factors related to H1N1 infection in school‐aged children. Methods This study analyzed data collected on 7448 school‐aged children in South Korea between 18 November and 8 December 2009. Results We found that H1N1 infection was associated with body mass index (BMI), waist circumference (WC), the use of facemasks, contact history with H1N1‐infected persons, and overseas travel history (P < 0·05). In addition, WC quartiles were significantly associated with H1N1 infection after adjusting for BMI and other confounding variables [OR (95% CI): 1·00, 1·10 (0·72–1·45), 1·13 (0·76–1·67), and 2·71 (1·74–4·24), respectively). Conclusions Abdominal obesity and the use of facemasks appear to be independently associated with H1N1 infection in school‐aged children. We infer that providing education on wearing facemasks and specific planning for abdominally obese children and adolescents may be effective means of reducing the spread of the influenza pandemic in school‐aged children.
Pitavastatin, a 3-hydroxyl-3-methylglutaryl-coenzyme A reductase inhibitor is distributed to the liver, a target organ of action and excreted mainly into the bile. To investigate the impact of influx (OATP1B1) and efflux (MRP2, BCRP) transporter alleles on its disposition, the pharmacokinetic (PK) parameters were compared among the following groups: SLCO1B1 (*15 carrier and non-carrier), ABCC2 (G1249A, C3972T, C-24T, G1549A, and G1774T), and ABCG2 (C421A) single nucleotide polymorphisms in 45 healthy Korean volunteers. Pitavastatin AUC(last) was higher in individuals carrying the SLCO1B1*15 allele than those not carrying it (144.1 ± 55.3 vs. 84.7 ± 25.7 h·ng/mL [mean ± SD], p = 0.002). The AUC(last) varied significantly according to the ABCC2 C-24T allele (103.4 ± 42.2, 80.2 ± 23.8, and 39.0 h·ng/mL in CC, CT and TT, respectively; p = 0.027). Other SNPs of ABCC2 and ABCG2 were not significant. The effect of these transporters and body weight on the AUC(last) and C(max) were tested, and only SLCO1B1 and ABCC2 C-24T genotypes were significant factors by analysis of covariance. These variants accounted for almost 50% of the variation in AUC(last) and C(max) of pitavastatin. Therefore, ABCC2 C-24T was significantly associated with pitavastatin human PK when the known effect of SLCO1B1*15 was also considered.
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