Nanotechnologies are being employed to enhance the stability and oral bioavailability of lipophilic substances, such as capsaicin. This study aimed to examine the pharmacokinetic properties of the formulated capsaicin-loaded nanoemulsions. A pharmacokinetic study was carried out using double-layer nanoemulsions fabricated with alginate and chitosan polymers and triple-layer nanoemulsions fabricated with chitosan/alginate polymers. Capsaicin nanoemulsions and capsaicin control (oleoresin capsicum) were administered to the rat at a dose of 10 mg/kg. A statistically significant difference was found in the area under the curve from time zero to time infinity (AUCinf) among formulations (p < 0.01). In comparison to the control group, the relative bioavailability of formulated nanoemulsions was up to 131.7. The AUCinf increased in a nano-size-dependent manner; as nano size decreased, AUCinf increased. IN comparison to the double-layer nanoemulsions, the triple-layer nanoemulsion showed a significantly increased volume of distribution, resulting in the increased clearance and decreased AUCinf. It was concluded that the formulated nanoemulsions could significantly enhance the bioavailabilty of capsaicin.

This study aimed to investigate the effects of polymorphisms of the flavin-containing mono-oxygenase 3 (FMO3) and flavin-containing mono-oxygenase 6 (FMO6) genes on the pharmacokinetics of sulindac sulfide, the active metabolite of sulindac, in patients with preterm labor. Ten single-nucleotide polymorphisms (SNPs) were genotyped, and plasma sulindac sulfide concentrations were measured at 0, 1.5, 4, and 10 hours after drug administration. The area under the curve from time 0 to the last sampling time point (AUC last ) for sulindac sulfide was obtained. The AUC last of sulindac sulfide was significantly higher in patients with variant-type homozygotes of FMO3 (rs909530) than those with ancestral alleles or heterozygotes. FMO3 (rs2266780) was in complete linkage disequilibrium with FMO6 (rs7885012), and there was marginal significance between the genotypes (P = 0.049). From multiple linear regression models, FMO3 (rs909530) was found to have significant influence on the AUC last of sulindac sulfide after adjusting for gestational age, weight, and all studied SNPs. The predictive contribution of rs909530 to the variability of sulindac sulfide AUC last was 27.0%. In conclusion, the results of this study could help clinicians predict the efficacies and side effects of sulindac in the development of individualized treatment of patients with preterm labor. IntroductionSulindac is a prostaglandin synthetase inhibitor (Nuki, 1983). As prostaglandin increase is observed in both term and preterm labor, prostaglandin inhibitors have been used as tocolytic agents (Karim, 1968). Sulindac contains a chiral sulfoxide moiety and is administered clinically as a racemate. It is an inactive prodrug and is reduced to a pharmacologically active metabolite, sulindac sulfide. Sulindac is also oxidized to an inactive metabolite, sulindac sulfone. The sulfide form is inactivated by flavin-containing mono-oxygenase 3 (FMO3), and the (S)-and (R)-sulindac sulfoxides are also oxidized to sulindac sulfone by FMO3 (Hamman et al., 2000;Hisamuddin and Yang, 2007).Several studies showed that FMO3 gene polymorphisms could result in interindividual and interethnic differences in FMO3 activity (Cashman and Zhang, 2002;Hernandez et al., 2003). The polymorphisms could result in differences in the pharmacokinetics and responses of drugs that are metabolized by FMO3, including sulindac. It was reported that genetic polymorphisms of FMO3 could affect clinical outcomes in patients with sulindac therapy due to adenomatous polypsis. The studied end points were pharmacodynamic responses such as polyposis prevention and regression (Hisamuddin et al., 2004(Hisamuddin et al., , 2005. However, there has been no study conducted on the effects of FMO3 genotypes on the blood concentrations of an active sulindac metabolite in clinical settings.It has been reported that flavin-containing mono-oxygenase 6 (FMO6) has significant sequence homology with FMO3 Hernandez et al., 2004;Hisamuddin and Yang, 2007). However, unlike FMO3, the study of the effects of FMO6...