Journal of pharmacological and toxicological methods
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J Pharmacol Toxicol Methods · Jul 2014
Comparative StudyComparison of two approaches of intestinal absorption by puerarin.
Everted gut sac (EGS) and in situ single-pass intestinal perfusion (SPIP) have been widely used in the study of drug absorption and biopharmaceutical classification systems (BCS). Furthermore, they could also be applied in the research of drug intestinal first-pass metabolism. Since most of Chinese herbal medicines (CHMs) are orally administrated, it is necessary to study the permeability of active ingredients of CHMs. Thus, we attempted to apply the EGS and SPIP models to study the permeability of puerarin, one of the active marker compounds (AMCs) of Puerariae Radix. ⋯ Three models for permeability were successfully practiced in the study of puerarin absorption and our research strategy will be useful for herbal constituent absorption in the future.
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J Pharmacol Toxicol Methods · Jul 2014
Translational PK/PD modeling for cardiovascular safety assessment of drug candidates: Methods and examples in drug development.
Cardiovascular toxicity is a significant cause of candidate failure in drug development. Pharmacokinetic/pharmacodynamic (PK/PD) modeling may reduce attrition by improving the understanding of the relationship between drug exposure and changes in cardiovascular endpoints. Diverse examples are discussed that elucidate how modeling can facilitate the interpretation of cardiovascular safety data in animals and enable quantitative translation of preclinical findings to man. ⋯ In this article, a range of PK/PD models are discussed that successfully described cardiovascular safety findings in the preclinical setting. Where clinical data were available, it was found that translational modeling enabled the accurate prediction of outcomes in man and facilitated the description of the therapeutic index. PK/PD modeling is thus demonstrated as a powerful tool to aid in the quantitative cardiovascular safety assessment of drug candidates and the optimization of early clinical study protocols.
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J Pharmacol Toxicol Methods · Jul 2014
Comparative StudyA vapourized Δ(9)-tetrahydrocannabinol (Δ(9)-THC) delivery system part II: comparison of behavioural effects of pulmonary versus parenteral cannabinoid exposure in rodents.
Studies of the rewarding and addictive properties of cannabinoids using rodents as animal models of human behaviour often fail to replicate findings from human studies. Animal studies typically employ parenteral routes of administration, whereas humans typically smoke cannabis, thus discrepancies may be related to different pharmacokinetics of parenteral and pulmonary routes of administration. Accordingly, a novel delivery system of vapourized Δ(9)-tetrahydrocannabinol (Δ(9)-THC) was developed and assessed for its pharmacokinetic, pharmacodynamic, and behavioural effects in rodents. A commercially available vapourizer was used to assess the effects of pulmonary (vapourized) administration of Δ(9)-THC and directly compared to parenteral (intraperitoneal, IP) administration of Δ(9)-THC. ⋯ These results suggest vapourized Δ(9)-THC administration produces behavioural effects qualitatively different from those induced by IP administration in rodents. Furthermore, vapourized Δ(9)-THC delivery in rodents may produce behavioural effects more comparable to those observed in humans. We conclude that some of the conflicting findings in animal and human cannabinoid studies may be related to pharmacokinetic differences associated with route of administration.