The disposition of debrisoquine in hypertensive patients

Br J Clin Pharmacol. 1978 Jan;5(1):27-34. doi: 10.1111/j.1365-2125.1978.tb01594.x.


1 The urinary recovery and plasma concentration of debrisoquine (D) and its metabolite 4-hydroxydebrisoquine (HD) has been studied following single and multiple oral administration of debrisoquine hemisulphate to 15 hypertensive in-patients and four normal volunteers.

2 Incremental doses and prolonged administration led to a proportionately greater urinary recovery and higher plasma concentration of D but the proportion recovered as HD fell while its plasma concentration remained unchanged. Dividing a dose or administering a single oral dose of D resulted in the formation of proportionately more HD and a lower urinary recovery of D. These findings suggest that the metabolism of D to HD may be partially saturated or inhibited by D itself or by HD.

3 Peak urinary excretion rates and plasma concentrations of both D and HD occurred 2 h after a single dose suggesting rapid absorption and presystemic metabolism.

4 HD was eliminated more rapidly than D. Mean (± s.d.) elimination half-life from the urine for HD was 9.6 ± 3.7 h and for D was 16.2 ± 5.7 h. Reasons for this are discussed.

5 Renal clearance of D and HD was not constant. A fall was observed with time after a single dose but on multiple dosing the clearance fell with increasing plasma concentrations. Mean (± s.d.) renal clearance values during multiple administration were D 282 ± 88 ml/min and HD 371 ± 178 ml/min. It is suggested that active saturable tubular secretion of D and HD may be responsible for their renal elimination.

6 The distribution of D in the blood was studied after a single dose to one volunteer. The greatest concentration of the drug was in the platelet rich fraction from which it was eliminated slowly. The elimination half-lives in plasma and platelet rich plasma were 17.5 h and 56 h respectively.

7 On early multiple dosing the hypotensive response was related to high plasma D concentrations.

MeSH terms

  • Adult
  • Blood Pressure / drug effects
  • Debrisoquin / administration & dosage
  • Debrisoquin / metabolism*
  • Debrisoquin / therapeutic use
  • Drug Administration Schedule
  • Food
  • Humans
  • Hypertension / drug therapy
  • Hypertension / metabolism*
  • Isoquinolines / metabolism*
  • Kidney / metabolism
  • Kinetics
  • Male


  • Isoquinolines
  • Debrisoquin