Differential effect of food on kinetics of bromocriptine in a modified release capsule and a conventional formulation.
The influence of food on release of drug from a modified release capsule of bromocriptine 5 mg (Parlodel SRO) and a conventional formulation of bromocriptine 5 mg has been studied in 8 healthy male volunteers. Both formulations produced objective and subjective effects, such as orthostatic reactions, nausea, dizziness, vomiting and nasal congestion. The modified release capsule caused fewer side-effects than the normal capsule. Both formulations had less cardiovascular effect in the fed than in the fasting state. There was no significant difference between the normal and the modified release capsules taken fasting or after a meal in terms of the AUC extrapolated to infinity. The relative bioavailability of the 5 mg modified release capsule was 84.6% of the normal capsule under fasting conditions and 107.5% after food. In contrast to the virtually unchanged extent of absorption, the rate of absorption was markedly affected by food, especially from the conventional capsule. The mean time of 50% absorption increased from 1.06 h (fasting) to 3.2 h (fed), whereas for the modified release capsule food mainly resulted in an increased lag time of absorption. The almost instantaneous dissolution of bromocriptine from the normal capsule in vitro (both in HCl and fasting human gastric juice) and the delay of absorption after a meal in vivo suggest that the rate limiting step in absorption of the normal capsules is delivery of released drug from the stomach to the small intestine, which is delayed by food. Both the modified release 5-mg capsule and the normal 5-mg capsule showed extended suppression of prolactin over 36 h, in all subjects, both fasted and after a meal.
Drewe
J
J
Drug Delivery System Department, Sandoz, Basle, Switzerland.
Mazer
N
N
Abisch
E
E
Krummen
K
K
Keck
M
M
D000328:Adult; D001682:Biological Availability; D001971:Bromocriptine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004361:Drug Tolerance; D005502:Food; D006801:Humans; D007024:Hypotension, Orthostatic / Q000139:chemically induced; D007408:Intestinal Absorption; D008297:Male; D011388:Prolactin / Q000097:blood
D003692:Delayed-Action Preparations; D001971:Bromocriptine; D011388:Prolactin