Background
Doryx MPC is a novel Mayne Pharma formulation of the oral tetracycline antimicrobial doxycycline. Doryx MPC has increased acid resistance compared to the standard Doryx tablet, which will minimise oesophageal and stomach dissolution and thus is anticipated to reduce irritation in those regions. The literature is presently void of a population pharmacokinetic analysis of doxycycline.
Aims
This study aimed to develop a population pharmacokinetic model of doxycycline plasma concentrations that could be used to assess the power of bioequivalence between Doryx® Delayed-Release tablets and Doryx MPC®.
Methods
Doxycyline pharmacokinetic data was avalible from eight phase 1 clinical trials following single / multiple doses of conventional release doxycycline capsules, Doryx® Delayed-Release tablets and Doryx MPC® under fed and fasted conditions. A population pharmacokinetic model was developed in a step-wise manner using NONMEM® 7.3. The final covariate model was developed according to a forward-inclusion (p<0.01) and then backward deletion (p<0.001) procedure.
Results
The final model was a two compartment model with two-transit absorption compartments. Structural covariates in the base model included formulation effects on relative bioavailability (F), absorption lag (ALAG) and the transit absorption rate (KTR) under the fed status. An absorption delay (lag) for the fed status (FTLAG2 = 0.203 h) was also included in the model as a structural covariate. The fed status was observed to decrease F by 10.5%, and the female sex resulted in a 14.4% increase in clearance.
Conclusions
This manuscript presents the first population pharmacokinetic model of doxycycline plasma concentrations following oral doxycycline administration. The model was used to assess the power of bioequivalence between Doryx® Delayed-Release tablets and Doryx MPC®, and it could potentially be used to critically examine and optimise doxycycline dose regimens.