Purpose

To explore the application of the parameters of the physiologically based finite time pharmacokinetic (PBFTPK) models subdivided in first-order (PBFTPK)₁ and zero-order (PBFTPK)₀ models to bioavailability and bioequivalence. To develop a methodology for the estimation of absolute bioavailability, F, from oral data exclusively.

Methods

Simulated concentration time data were generated from the Bateman equation and compared with data generated from the (PBFTPK)₁ and (PBFTPK)₀ models. The blood concentration C_b(τ) at the end of the absorption process τ, was compared to C_max; the utility of \( {(AUC)}_0^{\tau } \) and \( {(AUC)}_t^{\infty } \) in bioequivalence assessment was also explored. Equations for the calculation of F from oral data were derived for the (PBFTPK)₁ and (PBFTPK)₀ models. An estimate for F was also derived from an areas proportionality using oral data exclusively.

Results

The simulated data of the (PBFTPK)₀ models exhibit rich dynamics encountered in complex drug absorption phenomena. Both (PBFTPK)₁ and (PBFTPK)₀ models result either in C_max = C_b(τ) or C_max > C_b(τ) for rapidly- and not rapidly-absorbed drugs, respectively; in the latter case, C_b(τ) and τ are meaningful parameters for drug’s rate of exposure. For both (PBFTPK)₁ and (PBFTPK)₀ models, \( {(AUC)}_0^{\tau } \) or portions of it cannot be used as early exposure rate indicators. \( {(AUC)}_{\tau}^{\infty } \) is a useful parameter for the assessment of extent of absorption for very rapidly absorbed drugs. An estimate for F for theophylline formulations was found close to unity.

Conclusion

The (PBFTPK)₁ and (PBFTPK)₀ models are more akin to in vivo conditions. Estimates for F can be derived from oral data exclusively.

中文翻译：

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修订口服药物吸收的药代动力学：II 生物利用度-生物等效性考虑

目的

探讨基于生理的有限时间药代动力学（PBFTPK）模型的参数在生物利用度和生物等效性中的应用，该模型分为一级（PBFTPK）₁ 和零级（PBFTPK）₀ 模型。开发一种专门从口服数据估计绝对生物利用度F的方法。

方法

模拟浓度时间数据由 Bateman 方程生成，并与 (PBFTPK) ₁ 和 (PBFTPK) ₀ 模型生成的数据进行比较。将吸收过程 τ 结束时的血液浓度C _b (τ)与C _max进行比较；还探讨了\( {(AUC)}_0^{\tau } \) 和\( {(AUC)}_t^{\infty } \)在生物等效性评估中的效用。_{对于 (PBFTPK) 1} 和 (PBFTPK) ₀ 模型，导出了从口头数据计算F的方程。对F的估计也来自仅使用口头数据的区域比例。

结果

(PBFTPK) ₀ 模型的模拟数据表现出在复杂的药物吸收现象中遇到的丰富动力学。(PBFTPK) ₁ 和 (PBFTPK) ₀ 模型分别导致快速吸收药物和非快速吸收药物的C _max  = C _b (τ)或C _max  > C _b (τ) ；在后一种情况下，C _b (τ)和 τ 是药物暴露率的有意义的参数。对于 (PBFTPK) ₁ 和 (PBFTPK) ₀ 模型，  \( {(AUC)}_0^{\tau } \) 或其部分不能用作早期曝光率指标。\( {(AUC)}_{\tau }^{\infty } \) 是评估快速吸收药物吸收程度的有用参数。发现茶碱制剂的F估计值接近一致。

结论

(PBFTPK) ₁ 和 (PBFTPK) ₀ 模型更类似于体内条件。F的估计值只能从口头数据中得出。