Pharmacokinetics, safety, and tolerability of Pentoxifylline intravaginal gel for subfertile/infertile couples with low sperm quality: phase I randomized controlled clinical trial in healthy women

Abstract

Infertility is a global public health issue, attributable to male factors in 30%-50% of cases. By 2025, almost 10 million couples will encounter problems in having a baby. In assisted reproduction, Pentoxifylline improves sperm motility both in vitro and after oral administration in patients with asthenozoospermia. In this phase I dose escalation study, we aimed to assess the pharmacokinetics, safety, and tolerability of three doses of Pentoxifylline formulated as a gel (PKB171 gel) for intravaginal administration in healthy female volunteers and to determine the maximum tolerated dose (MTD) after single doses of 100 mg, 150 mg or 200 mg of Pentoxifylline, following by an extension substudy involving multiple-dose vaginal administration. For both studies, the main variable was the incidence of adverse events (AEs) after each dose. In the single dose study, plasma concentrations of Pentoxifylline and 5-Hydroxy Pentoxifylline were determined at baseline and at +10, +20, +30, +45 minutes, +1, +2, +4, +8 and +12 hours after dose. Vaginally administered PKB171 gel at all study doses was well-tolerated and MTD was 200 mg. The incidence of AEs did not increase as a function of dose. Linearity in Pentoxifylline and 5-Hydroxy Pentoxifylline plasma concentrations was observed for the three doses studied.