Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data

Area of Science:

• Pharmacokinetics
• Drug Metabolism and Disposition
• Clinical Pharmacology

Background:

• Limited population pharmacokinetic (PopPK) analysis exists for doxycycline.
• Understanding doxycycline pharmacokinetics is crucial for optimizing therapeutic use and ensuring bioequivalence of different formulations.

Purpose of the Study:

• To develop and validate a PopPK model for doxycycline plasma concentrations.
• To assess the bioequivalence between Doryx delayed-release tablets and Doryx MPC using the developed model.
• To identify covariates influencing doxycycline pharmacokinetics.

Main Methods:

• Utilized pharmacokinetic data from eight Phase 1 clinical trials involving various doxycycline formulations and conditions.
• Employed NONMEM (version 7.3) for stepwise model development using forward inclusion and backward deletion procedures.
• Developed a two-compartment model with two-transit absorption compartments, incorporating structural covariates.

Main Results:

• The final PopPK model identified formulation and fed status as significant factors affecting relative bioavailability (F) and absorption lag (ALAG).
• Fed status decreased F by 10.5%, while female sex increased clearance by 14.4%.
• The model successfully assessed bioequivalence power between Doryx delayed-release and Doryx MPC.

Conclusions:

• This study presents the first PopPK model for oral doxycycline administration.
• The model provides a valuable tool for evaluating bioequivalence and potentially optimizing doxycycline dosage regimens.
• The findings highlight the impact of formulation and patient factors on doxycycline pharmacokinetics.