Co-administration of oral sarecycline with high-fat food does not significantly affect clinical efficacy of the drug in patients with acne, and weight-based dosing of the third-generation tetracycline-class antibiotic with or without food appears feasible, according to study findings published in Dermatologic Therapy.
To examine weight-based dosing strategies as well as the effect of food intake on absorption and clinical efficacy of sarecycline, a team of researchers investigated data from 12 clinical trials using population pharmacokinetic (PPK) modeling, exposure-response (E-R) modeling, and pharmacodynamic data. The PPK modeling included 562 patients with acne vulgaris from the 12 clinical trials. Phase 1 trials provided data for healthy participants.
In an analysis unadjusted for bioavailability, the estimated apparent clearance was 3.15 L/hour (relative standard error [RSE], 2.11%). In addition, the estimated V1/F and apparent peripheral volume of distribution (V2/F) values were 54.2 L (RSE, 2.63%) and 15.1 L (RSE, 6.48%), respectively. The estimated ka was 3.45 h-1 (RSE, 16.0%).
According to the investigators, predictors of both F and ka included prandial state and dose. The estimated exponent of the normalized weight effect (CL/FWT) was 0.291. In the simulation experiment, dosing adjustment by body weight reportedly led to “similar differences” in the peak drug levels among all weight groups when compared with a 100-mg dose strategy.
In the E-R model, the researchers assessed inflammatory lesion counts with time, drug exposure, and placebo effects. The researchers considered the inflammatory lesion counts over 12 weeks as a continuous variable and examined this variable with an indirect response model that included the drug effect on the production of lesion counts. The researchers also evaluated the association between Investigator’s Global Assessment response and sarecycline exposure (AUCss) as well as other participant characteristics with logistic regression methods.
The researchers wrote that a combined simulation of pharmacokinetic data and E-R models demonstrated support for sarecycline administration with or without food. In phase 3 trial participants, the investigators observed a relatively flat exposure efficacy relationship over a range of concentrations. Sarecycline co-administration with a high-fat meal led to an estimated 21.7% reduction in exposure at a steady state as well as a reduced response of 0.9 inflammatory lesions, according to the researchers, but the reduction in lesion count was not considered clinically relevant.
In their conclusion, the researchers suggested that “given the additional benefit that sarecycline is administered daily with or without food, the convenience provided for the patient and the clinician are both highly favorable.”
Disclosure: This clinical trial was supported by Almirall LLC. Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.
Grada A, Del Rosso JQ, Graber E, et al. Sarecycline treatment for acne vulgaris: Rationale for weight-based dosing and limited impact of food intake on clinical efficacy. Dermatol Ther. Published online December 19, 2021. doi:10.1111/dth.15275