Influence of vitamin C on the absorption and first pass metabolism of propranolol.
The effect of ascorbic acid on the availability of propranolol has been examined. After oral administration of propranolol 80 mg with or without ascorbic acid pretreatment (2 g), the plasma concentrations and urinary excretion of propranolol and its metabolites, 4-hydroxy-propranolol and propranolol-conjugated, were determined by HPLC. Compared to controls, vitamin C decreased the maximum concentration of propranolol from 463 to 334 nmol.l-1, and the area under the propranolol concentration-time curve (from 0 to 24 hours) from 3.13 to 1.96 mumol.l-1.h. The time to reach maximum propranolol concentration was increased from 1.9 to 2.7. The total amount of drug recovered in urine has also significantly diminished (from 12.6 to 4.29 mg). No change in elimination rate was observed, indicating that ascorbic acid had affected both the absorption process and the first pass metabolism. The heart-rate decreased less when propranolol was administered with ascorbic acid in comparison to control subjects, although this interaction has little biological importance.
Gonzalez
J P
JP
Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Vizcaya, Spain.
Valdivieso
A
A
Calvo
R
R
Rodríguez-Sasiaín
J M
JM
Jimenez
R
R
Aguirre
C
C
du Souich
P
P
D000284:Administration, Oral; D000328:Adult; D001205:Ascorbic Acid / Q000494:pharmacology*; D001682:Biological Availability; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D010599:Pharmacokinetics; D011433:Propranolol / Q000378:metabolism*; D013997:Time Factors; D014838:Volunteers
D011433:Propranolol; D001205:Ascorbic Acid