Doses and dosage intervals of drugs—clinical practice and pharmacokinetic principles

Abstract

Outpatient prescriptions dispensed to 17,000 individuals in the county of Jämtland, Sweden, have been analyzed with regard to doses and dosage schedules. Two groups of drugs were studied; one group with marked interindividual variability in metabolism (antidepressants, beta receptor blockers, and phenytoin), the other group excreted unchanged in the urine (digoxin, nitrofurantoin, sulfonamides, and tetracycline). A 25-fold—15-fold variability in daily doses wasfoundfor amitriptyline and nortriptyline, respectively. Four-Jifths ofthe prescriptions were for doses between 30 and 75 mg, making the mean dose remarkably low—58 and 48 mg, respectively. The variability in doses was high er for the beta receptor blockers propranolol and alprenolol. Daily doses of phenytoin varied between 0.1 and 0.6 gm, 93% of the doses falling between 0.2 and 0.4 gm. Generally, doses of sulfonamides and nitrofurantoin prescribed to children were correctly reduced. In the elderly the doses of these drugs and of tetracycline and digoxin were only moderately reduced in discrepancy with the physiologic impairment of kidney function. The clinical significance of these findings has not been evaluated. The effect of drug information programs on dosage intervals prescribed for procainamide, phenytoin, and beta receptor blocking drugs is demonstrated. It is suggested that more emphasis be given to general pharmacokinetic principles in drug information programs.