奥罗斯控释效果交付oxybutynin氯的药代学和药效学。

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Sathyan G,总理MB, Gupta SK

奥罗斯控释效果交付oxybutynin氯的药代学和药效学。

Br中国新药杂志。2001年10月,52(4):409 - 17所示。doi: 10.1046 / j.0306-5251.2001.01463.x。

PubMed ID
11678784 (在PubMed
]
文摘

未标记的:目的:口干是一种常见的副作用与速释oxybutynin (IR-Oxy)。Ditropan XL [(Oxy-XL),氯化oxybutynin的缓释制剂,每日一口服剂型,结合了奥罗斯的技术。口干的药效学指标Oxy-XL IR-Oxy管理局之间的比较。稳态立体定向药物动力学也建立了两个配方和kinetic-dynamic oxybutynin关系检查。反复给药方法:这是一项随机,双盲,两种治疗,两年期,交叉研究。基线评估的一天后,志愿者被随机分配到两种治疗序列和接收4天的治疗治疗之间的洗脱期7天。治疗:1)Oxy-XL早上10毫克和安慰剂8 h后,和2)IR-Oxy 5毫克早上8 h后。志愿者评估口干严重主观使用100毫米视觉模拟量表,血管(基线、治疗天1和4),客观地收集唾液(基线和治疗第四天)早晨剂量后在剂量和每小时大约16 h。几个收集血液样本在每个治疗,频繁采样4天为等离子体分析R - S-oxybutynin和R - S-desethyloxybutynin浓度。结果:相对稳定等离子体浓度oxybutynin及其代谢物被认为在24 h后Oxy-XL政府与波动的程度更低(P = 0.001;l减少66%到81%比IR-Oxy各种分析物)。 Compared with IR-Oxy, Oxy-XL yielded higher (131% and 158% for the R- and S-isomer, respectively) oxybutynin and lower (62% and 78% for the R- and S-isomer, respectively) desethyloxybutynin bioavailability, suggesting reduced first-pass metabolism. Saliva output (area under the effect curve) was significantly higher [P = 0.001; 37% (95% confidence interval: 24, 51%)] with Oxy-XL than with IR-Oxy and, accordingly, dry mouth severity (VAS) integrated over the day was significantly lower with Oxy-XL. The decrease in saliva output and the consequent increase in dry mouth severity correlated with the metabolite R-desethyloxybutynin concentration, and no apparent relationship was observed with the R-oxybutynin concentration. This suggests that the metabolite may contribute to the dry mouth. Therefore, the reduction in metabolite exposure with Oxy-XL may be a possible explanation for the observed decrease in dry mouth severity with OXY-XL compared with IR-Oxy. CONCLUSIONS: Oxy-XL maintains relatively constant plasma drug and metabolite concentrations and minimizes first-pass metabolism of oxybutynin. The metabolite appears to contribute to dry mouth associated with oxybutynin, and following Oxy-XL metabolite exposure is reduced compared with IR-Oxy. Consequently less dry mouth was observed with Oxy-XL as compared with IR-Oxy.

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