The relative bioavailability of metoprolol following oral and rectal administration to volunteers and patients.
The pharmacokinetics, efficacy and safety of metoprolol tartrate 25 mg fatty suppositories were studied in 5 healthy volunteers and in 8 patients suffering from instable angina pectoris. Metoprolol 25 mg capsules were used as a control oral dosage form. Metoprolol showed a considerable rectal bioavailability (AUC, C max) and was absorbed quickly from the rectum (T max). In both groups rectal bioavailability was comparable. However, oral bioavailability was much lower in the volunteer group than in the patient group. Furthermore, ratios of metoprolol/alpha-OH-metoprolol concentrations in plasma and urine gave an indication for a partial avoidance of the first pass effect after rectal administration. Further research is necessary to define an exact rectal dosage of metoprolol. In all patients, a substantial drop in heart rate, systolic and diastolic blood pressure was seen after administration of the first suppository. Metoprolol suppositories appear to be an effective, safe and suitable alternative for patients who are in need for beta blocking medication and who are unable to take oral medication for a certain amount of time.
de Stoppelaar
F M
FM
Department of Clinical Pharmacy and Toxicology, University Hospital Maastricht, The Netherlands.
Stolk
L M
LM
Beysens
A J
AJ
Stappers
J L
JL
Gorgels
A P
AP
D000284:Administration, Oral; D000285:Administration, Rectal; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000328:Adult; D000789:Angina, Unstable / Q000378:metabolism*; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008790:Metoprolol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008875:Middle Aged; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D008790:Metoprolol