Pharmacokinetics of a novel surface‐active agent, purified poloxamer 188, in rat, rabbit, dog and man

Abstract

Purified poloxamer 188 (PP188) is a non-ionic, block copolymer surfactant that is currently being evaluated clinically in sickle cell disease vaso-occlusive crisis and acute chest syndrome and preclinically in spinal cord injury and muscular dystrophy. This paper describes the pharmacokinetics of PP188 in rats, pregnant rats, pregnant rabbits, dogs and humans. Plasma protein binding interaction studies demonstrated no clinically significant effects on narcotic analgesics, hydroxyurea, warfarin, diazepam or digitoxin, but an increase in free fraction for propranolol. The plasma concentrations increased proportionate with increasing dose in all species tested. Renal clearance accounted for 90% of total plasma clearance in man. A single metabolite was detected and quantified in the plasma from dogs and humans that was cleared more slowly than parent drug. Allometric scaling of plasma clearance and volume of distribution at steady-state (Vss) across species provided good predictions of the pharmacokinetic parameters in humans. Based on the comparative pharmacokinetics of PP188 in rat, rabbit, dog and man, all three animal species were appropriate models for evaluating various aspects of PP188's toxicological profile.

Bioavailability Effect of Methylprednisolone by Polymeric Micelles

“…In addition, by coating with PEO or PEO-PPO-PEO, a number of studies have demonstrated the Fstealth_ behavior of delivery that decreased the uptake or degradation by the reticuloendothelial system (RES) or reduced the adsorption by plasma proteins (43)(44)(45)(46). Our in vivo pharmacokinetic data (Fig.…”

Poloxamer 188 Facilitates The Repair Of Alveolus Resident Cells In Ventilator Injured Lungs

“…Headache, nausea, and back and leg pain have been reported in humans enrolled in pharmacokinetic studies (15,37,38). P188 was used as an emulsifying agent in perfluorocarbon artificial blood, but its use was abandoned because of a high rate of adverse reactions including hypotension, hypoxemia, pulmonary hypertension, and neutropenia (39)(40)(41).…”

Effects of poloxamer 188 on human PMN cells

“…P188 has shown promise in the management of many diseases, including sickle cell disease, vascular disease, stroke, and cancer, and clinical trials, involving more than 4,000 patients, have shown it to be safe when administered intravenously. 5–7 P188 has shown the ability to improve the microcirculation 8 , minimize platelet aggregation 9 , and improve survival after hemorrhagic shock. 10 P188 has also shown the ability to mitigate reperfusion injury after myocardial infarction 11, 12 and improve hemodynamics, and subsequent oxygen delivery, after hemorrhagic shock in humans.…”