Pharmacokinetics

Absorption: For treatment of erectile dysfunction, alprostadil is administered by injection into the corpora cavernosa. The absolute bioavailability of alprostadil has not been determined.

Distribution: Following intracavernosal injection of 20 micrograms alprostadil, mean peripheral plasma concentrations of alprostadil at 30 and 60 minutes after injection (89 and 102 picograms/milliliter, respectively) were not significantly greater than baseline levels of endogenous alprostadil (96 picograms/milliliter). Alprostadil is bound in plasma primarily to albumin (81% bound) and to a lesser extent alpha-globulin IV-4 fraction (55% bound). No significant binding to erythrocytes or white blood cells was observed.

Metabolism: Alprostadil is rapidly converted to compounds which are further metabolized prior to excretion. Following intravenous administration, approximately 80% of circulating alprostadil is metabolized in one pass through the lungs, primarily by beta- and omega-oxidation. Hence, any alprostadil entering the systemic circulation following intracavernosal injection is very rapidly metabolized. Following intracavernosal injection of 20 micrograms alprostadil, peripheral levels of the major circulating metabolite, 13,14-dihydro-15-oxo-PGE₁, increased to reach a peak 30 minutes after injection and returned to pre-dose levels by 60 minutes after injection.

Excretion: The metabolites of alprostadil are excreted primarily by the kidney, with almost 90% of an administered intravenous dose excreted in urine within 24 hour post-dose. The remainder of the dose is excreted in the feces. There is no evidence of this tissue retention of alprostadil or its metabolites following intravenous administration.

Pharmacokinetics in Special Populations

Geriatric: The potential effect of age on the pharmacokinetics of alprostadil has not been formally evaluated. In patients with acute respiratory distress syndrome (ARDS), the mean (±SD) pulmonary extraction of alprostadil was 72% ± 15% in 11 elderly patients aged 65 years or older (mean 71 ± 6 years) and 65% ± 20% in 6 young patients aged 35 years or younger (mean, 28 ± 5 years).

Pediatric: Alprostadil plasma concentrations were measured in 10 neonates (gestational age of 34 weeks in 2 infants and 38 to 40 weeks in 8 infants) receiving steady-state intravenous infusions of alprostadil to treat underlying cardiac malformations. Infusion rates of alprostadil ranged from 5 to 50 (median, 45) nanograms/kilogram/minute, resulting in alprostadil plasma concentrations ranging between 22 and 530 (median, 56) picograms/milliliter. The wide range of alprostadil plasma concentrations in neonates reflects high variability in individual clearances of alprostadil in this patient population.

Gender: The potential influence of gender on the pharmacokinetics of alprostadil has not been formally studied in healthy subjects. Two studies determined the pulmonary extraction of alprostadil following intravascular administration in 23 patients with ARDS. The mean (±SD) pulmonary extraction was 66% ± 20% in 17 male patients and 69% ± 18% in 6 female patients, suggesting that the pharmacokinetics of alprostadil are not influenced by gender.

Race: The potential influence of race on the pharmacokinetics of alprostadil has not been formally evaluated.

Renal and Hepatic Insufficiency

Pulmonary first-pass metabolism is the primary factor influencing the systemic clearance of alprostadil. Although the pharmacokinetics of alprostadil have not been formally examined in patients with renal or hepatic insufficiency, alterations in renal or hepatic function would not be expected to have a major influence on the pharmacokinetics of alprostadil.

Pulmonary Disease

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