Alprostadil

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Medicines administered to the neonate [c]

115-116 °C

115 - 116 °C

4.87

4.85 (at 25 °C)

190.6 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Calculation: Single Field; Dataset: Oxylipins]

198.3 Ų [M+Na]+ [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P264, P270, P280, P301+P316, P318, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 74 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The use of alprostadil for the treatment of erectile dysfunction in males may lead to prolonged erections and, in some cases, priapism. The incidence of priapism as an adverse effect of alprostadil is more common with the intraurethral suppository. This condition can also occur when unauthorized combination therapy is used or when patients exceed the prescribed dosage.

G04BE01

G - Genito urinary system and sex hormones

C - Cardiovascular system

QG - Genito urinary system and sex hormones

QC - Cardiovascular system

C01EA01

Prostaglandin E1 is produced endogenously to relax vascular smooth muscle and cause vasodilation. As a synthetic form of prostaglandin E1, alprostadil has the same pharmacodynamic effects. Alprostadil inhibits platelet aggregation, has anti-inflammatory effects, interferes with immune responses, and stimulates factor X, a blood coagulation enzyme. In adult males, the use of alprostadil may lead to prolonged erection and priapism, penile fibrosis, hypotension, and injection site bleeding. In patients treated up to 24 months with alprostadil, the incidence of prolonged erections (>4 hours long) was 4% of all, and the incidence of priapism (erections greater than 6 hours in duration) was <1%. Patients with preexisting cardiovascular disease treated with alprostadil may also have higher cardiac risk. Neonates with congenital heart defects treated with alprostadil may experience apnea. Apnea is experienced by 10-12% of neonates and is more common in those weighing less than 2 kg at birth. The administration of alprostadil to neonates may also result in gastric outlet obstruction secondary to antral hyperplasia.

Alprostadil is a smooth muscle relaxant that promotes vasodilation and platelet aggregation inhibition. In neonatal patients with ductus arteriosus patency, alprostadil relaxes the ductus arteriosus (DA) smooth muscle, preventing or reversing the functional closure of the DA that occurs shortly after birth. This results in increased pulmonary or systemic blood flow in infants. Alprostadil appears to be most effective within 96 hours after birth since the DA rapidly loses its responsiveness to alprostadil. When administered by intracavernosal injection or as an intraurethral suppository, alprostadil acts locally to relax the trabecular smooth muscle of the corpora cavernosa and the cavernosal arteries. Swelling, elongation, and rigidity of the penis result when arterial blood rapidly flows into the corpus cavernosum to expand the lacunar spaces. The entrapped blood reduces the venous blood outflow as sinusoids compress against the tunica albuginea leading to penile rigidity. This is referred to as the corporal veno-occlusive mechanism.

Alprostadil is rapidly metabolized in the human body. Following intracavernous administration, alprostadil is metabolized in the corpus cavernosum, and a smaller portion is absorbed from the penis into systemic circulation. After intravenous or arterial administration, alprostadil is metabolized and distributed throughout the entire body except for the central nervous system. As much as 60-90% of the circulating alprostadil may be metabolized in the lungs through first-pass pulmonary elimination, in a process known as beta- and omega-oxidation. The enzymatic oxidation of the C15-hydroxy group of alprostadil leads to the formation of 15-keto-PGE₁, while the reduction of the C13, 14-double bond produces 15-keto-PGE₀, and 13,14-dihydro-PGE₁ (PGE₀). The 15-keto metabolites are inactive, but the PGE₀ metabolite has a similar potency to alprostadil in isolated animal organs. The major metabolite of alprostadil is 15-keto-PGE₀.

F5TD010360

ALPROSTADIL

Physiologic Effects [PE] - Genitourinary Arterial Vasodilation

Established Pharmacologic Class [EPC] - Prostaglandin Analog

Established Pharmacologic Class [EPC] - Prostaglandin E1 Agonist

Mechanisms of Action [MoA] - Prostaglandin Receptor Agonists

Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.

Drugs used to cause dilation of the blood vessels.

Drugs used in the treatment of urological conditions and diseases such as URINARY INCONTINENCE and URINARY TRACT INFECTIONS.

In patients with erectile dysfunction given 20 μg of alprostadil intracavernously, the systemic plasma concentrations of prostaglandin E1 increased from a baseline of 0.8 pg/mL to a Cmax of 16.8 pg/mL (corrected for baseline). The tmax and AUC for this group of patients were 4.8 min and 173 pg⋅min/mL, respectively. In patients given 20 μg of alprostadil intravenously, AUC was similar to the one detected in patients that received alprostadil intracavernously (174 pg⋅min/mL); however, they had a higher tmax (25.5 min) and a lower Cmax (7.09 pg/mL). Compared to the same dose given by a short-term intravenous infusion, the absolute bioavailability of alprostadil estimated from systemic exposure was about 98%.

Following the degradation of alprostadil by beta- and omega-oxidation, metabolites are excreted primarily by the kidney, and excretion is essentially complete within 24 hours after administration (92%). Approximately 88% and 12% of alprostadil metabolites are excreted through urine and feces, respectively, over 72 hours. Alprostadil and its metabolites are not retained in tissues, and unchanged alprostadil has not been detected in urine.

The volume of distribution of alprostadil has yet to be determined.

In patients with erectile dysfunction given an intravenous infusion of alprostadil (20 μg), the total body clearance was 115 L/min.