Absorption kinetics of dihydroergotoxine following oral administration to man.

Abstract

The absorption characteristics of dihydroergotoxine administered as an oral solution, tablet and retard capsule have been determined in a randomised cross‐over investigation in 12 healthy males. The plasma concentrations of dihydroergotoxine produced by the three preparations, measured using a specific and sensitive radioimmuno‐assay method over 24 h, exceeded 200 pg ml‐1 for approximately 5 h and decayed in a biphasic manner with a slowest measured half‐life of 12‐14 h. The retard capsule differs from the other two preparations in having a low Cmax (50% of that recorded for the solution) and a clearly defined plateau. The bioavailability of the retard capsule was similar to that for the solution indicating that first‐pass metabolism is not significantly increased following a three‐fold prolongation in the absorption rate constant. The 20‐40% greater bioavailability of dihydroergotoxine solution and retard capsule in comparison with the standard tablet may be due to a reduced contact time with gastric secretions achieved by means of rapid absorption from the stomach (solution) or delayed release at pH 1.5 (retard capsule).

Clinical pharmacokinetics of the nifedipine/co-dergocrine combination in impaired liver and renal function

“…In healthy males, Woodcock et aI. (18) reported elimination half-lives of 2.6 ± 1.6 h comparable to our control group. However, it has to be kept in mind that due to the limit of detection plasma concentrations could not be analyzed in all patients 36 h after dosing.…”

Bioavailability and Pharmacokinetic Profile of Dihydroergotoxine from a Tablet and from an Oral Solution Formulation

“…Nevertheless the radioimmuno-assay methods are still the most practicable and reliable methods, not only for their high sensitivity but also because they conglobe the information on the cloud of parent substances and metabolites which are responsible for the therapeutic effects of DHETM [9,16]. The evidence gathered with the available methods that include the use of radiolabelled DHETM, shows that orally administered DHETM is rapidly but incompletely absorbed and undergoes to a notable first-pass metabolism in the liver, with a final bioavailability of the parent substance of 8 %−25 % [4,8,17]. The peak concentrations are reached after 1−3 h [17].…”

“…The evidence gathered with the available methods that include the use of radiolabelled DHETM, shows that orally administered DHETM is rapidly but incompletely absorbed and undergoes to a notable first-pass metabolism in the liver, with a final bioavailability of the parent substance of 8 %−25 % [4,8,17]. The peak concentrations are reached after 1−3 h [17]. The elimination half-life from blood is biphasic with 2 and 12 to 20 h, respectively.…”