The Variability in the Pharmacokinetics of Follitropin Alfa: A Systematic Review

Despite extensive research on the pharmacodynamics of follitropin alfa, a comprehensive synthesis of its pharmacokinetic variability is lacking. Understanding the interindividual and intraindividual variability in the pharmacokinetics of follitropin alfa may help inform dosing strategies by reducing variability in systemic exposure. This systematic review aimed to characterise the variability in the pharmacokinetics of follitropin alfa. Embase, PubMed, Scopus and citation mining of included articles were searched from database inception to 10 November 2025. Studies performed in humans, published in English which reported the pharmacokinetics, route of administration and dosing regimen of follitropin alfa were eligible for inclusion. Fifteen eligible studies were evaluated. The pharmacokinetics of follitropin alfa were described by a two-compartment model following intravenous administration, and a one-compartment model with first-order absorption after intramuscular or subcutaneous administration. Follitropin alfa exhibited dose-proportional pharmacokinetics. Moderate interindividual variability (26–42%) in apparent clearance was reported following multiple subcutaneous administrations. Body weight influenced the pharmacokinetics of subcutaneously administered follitropin alfa. Comparable pharmacokinetic characteristics of follitropin alfa were observed across (i) originator and biosimilar preparations, (ii) healthy and infertile individuals, and (iii) subcutaneous and intramuscular routes of administration. Weight-based dosing of follitropin alfa may reduce pharmacokinetic interindividual variability. However, whether this reduction in variability translates into more consistent ovarian response remains unclear and requires further investigation.