Kokubun Hideya, Ebinuma Keiichi, Matoba Motohiro, Takayanagi Risa, Yamada Yasuhiko, Yago Kazuo
Department of Pharmacy, Kitasato University Hospital, Minami-ku, Kanagawa, Japan.
J Pain Palliat Care Pharmacother. 2012 Jun;26(2):98-104. doi: 10.3109/15360288.2012.679725.
Determining the appropriate dose of transdermal fentanyl (TDF) for the alleviation of cancer pain requires determining the factors causing variations in serum fentanyl concentration after TDF treatment. The objective of this study was to identify these factors and incorporate them into a formula that can be used to predict serum fentanyl concentration after application of a TDF patch. Blood samples of cancer patients treated with a TDF patch for the alleviation of pain were collected at 24, 48, and 72 hours after application to evaluate population pharmacokinetics using the nonlinear mixed-effect model (NONMEM). Based upon this evaluation, Child-Pugh Score and use of a cytochrome P450 3A4 (CYP3A4) inducer were identified as the most significant factors in variations in serum fentanyl concentration and incorporated into the following Final Model formula: CL(fenta) (L/h) = 3.53 × (15 - Child-Pugh Score) × (1 + 1.38 × use or no use of CYP3A4 inducer). Bootstrap evaluation of the Final Model revealed a high convergence rate, suggesting that the model formula is a reliable and useful tool for determining TDF dose for the alleviation of cancer pain.
确定用于缓解癌痛的透皮芬太尼（TDF）的合适剂量，需要确定TDF治疗后导致血清芬太尼浓度变化的因素。本研究的目的是识别这些因素，并将其纳入一个可用于预测TDF贴片应用后血清芬太尼浓度的公式中。对使用TDF贴片缓解疼痛的癌症患者，在贴片应用后24、48和72小时采集血样，使用非线性混合效应模型（NONMEM）评估群体药代动力学。基于该评估，Child-Pugh评分和细胞色素P450 3A4（CYP3A4）诱导剂的使用被确定为血清芬太尼浓度变化的最显著因素，并纳入以下最终模型公式：CL（芬太）（L/h）= 3.53×（15 - Child-Pugh评分）×（1 + 1.38×使用或未使用CYP3A4诱导剂）。对最终模型的自举评估显示收敛率很高，这表明该模型公式是确定用于缓解癌痛的TDF剂量的可靠且有用的工具。
