IR alfuzosin is rapidly and well absorbed after oral administration. The mean time to peak serum concentration of alfuzosin is 1.5 hours after an oral dose.[23,24] Improved peak and mean urine flow rates have been documented within 1.5 hours of administration of an oral dose. Its oral bioavailability is 64%, and its absorption is not affected by food. Therefore, alfuzosin can be taken without regard to meals.
An ER formulation of alfuzosin, Geomatrix, was developed by Jagotec AG. The three-layered tablet includes a hydrophilic matrix core of active drug and two inert layers that control the rate of drug release from the core. This slows the dissolution of the drug in the matrix core and slows absorption of alfuzosin from the dosage form. The areas under the curve for the bioavailability of 10-mg ER formulations of alfuzosin were similar to those of IR 2.5-mg thrice daily and 5-mg twice daily alfuzosin tablets.[28,29] Although direct comparison studies of 5-mg ER alfuzosin twice daily versus IR alfuzosin have not been conducted, such a study has been completed for 10-mg ER alfuzosin as a single daily dose versus 2.5-mg IR alfuzosin taken thrice daily. The latter formulations were found to be similar in clinical effectiveness.
Alfuzosin has a serum half-life of five hours after oral administration. Alfuzosin has a linear pharmacokinetic profile over the dosing range of 1 to 5 mg, with no change in half-life despite an increase in the dose.[23,26]
The volume of distribution of alfuzosin is 2.5 L/kg, and 90% of each dose is protein bound. Because the volume of distribution of alfuzosin is lower in some elderly patients, the initial dose in these patients should be conservative, using the smallest effective daily dose.
Alfuzosin undergoes extensive hepatic metabolism; however, its metabolism is not saturable. Only 11% of each dose is excreted by the kidneys as unchanged drug; 75-91% of alfuzosin metabolites are eliminated in feces and the rest is excreted in urine. Patients with liver failure should be started on the lowest daily dose and carefully monitored for adverse effects related to accumulation of the active drug. Dosage reduction may be necessary in these patients. Dosage modification is not required in patients with renal impairment.
Alfuzosin excretion in breast milk is not known at this time. Table 1 compares the pharmacokinetic profile of alfuzosin to that of other α1-adrenergic antagonists.
Am J Health Syst Pharm. 2003;60(14) © 2003 American Society of Health-System Pharmacists
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