Pertti Pentikäinen

The effect of spironolactone on antipyrine metabolism in man.

Spironolactone treatment was associated with a decrease in the plasma antipyrine half-life in all 9 volunteers studied. This was associated with an increased excretion of 4-OH antipyrine but not 3-hydroxymethyl antipyrine in their urine. The plasma antipyrine disappearance rate correlated with the excretion rate of 4-OH antipyrine in the urine. Spironolactone increased the excretion of 6-βOH cortisol in the urine. These data provided indirect evidence that spironolactone is an inducer of hepatic drug hydroxylation in man.

Association between clinical cardiac status, laboratory parameters, and digoxin usage

The cardiac glycosides are among the most effective drugs available for improving myocardial contractility. Their use, however, is not without hazard since a significant number of patients develop toxicity. 1, ~ Recent improvements in our knowledge of the pharmacology and therapeutic use of the digitalis glycosides should make our use of these drugs in patients more rational and decrease the number of toxic events. ~-3 The development of the digoxin radioimmunoassay 4, 5 has been particularly useful in this regard. There have been a number of studies which have evaluated the relationship between the serum digoxin concentration and clinical evidence of digoxin intoxication2 -19 With the exception of one study, ~9 all of these have demonstrated a significant positive relationship between the serum digoxin concentration and clinical evidence of glycoside intoxication. The present study was undertaken to evaluate the relationship between serum digoxin concentrations, other laboratory parameters, and the clinical response of patients receiving digoxin. In addition to defining a significant relationship

Bioavailability studies on para-aminosalicylic acid and its various salts in man. I. Absorption from solution and suspension

The relative bioavailability of PAS and the sodium, potassium, and calcium salts of PAS has been studied. Absorption of PAS and its three salts is essentially complete. Dissolution of PAS appears to be a rate-limiting factor in its absorption. The type of salt administered affects the rate of absorption. Although absorption of all four compounds was complete, the areas under the plasma concentration-time curve, or bioavailable drug, are dependent on the rate of absorption. The data presented show evidence of rate-limited metabolism, especially in the first pass.

A two-year crossover therapeutic trial with halofenate and clofibrate.

Twelve patients with Type IV hyperlipoproteinemia were treated with clofibrate and halofenate in a double blind, crossover trial for two years. Drug intake was monitored by determination of the level of the drugs in serum. Halofenate and clofibrate were equally effective in lowering plasma triglycerides and cholesterol levels. Patients who were secretors of ABO blood group antigens in saliva had a greater hypocholesterolemic response to both drugs than those who were nonsecretors. Clofibrate treatment resulted in a significant rise of low density lipoprotein cholesterol. Both drugs lowered serum bilirubin levels and this effect had a significant positive correlation with that on uric acid levels. Halofenate had a greater hypouricemic effect than clofibrate and may be a useful drug for treatment of patients with Type IV hyperlipoproteinemia who have concomitant hyperuricemia.

Pamatolol: Phase I evaluation of the pharmacodynamics of a cardioselective beta adrenoceptor blocking drug

A Phase I evaluation of a new beta adrenoceptor blocker, pamatolol, was performed in 10 healthy male volunteers, Minor reductions in standing and exercise and isoproterenol‐induced increases in heart rate were observed with the 10‐mg oral dose and appeared maximal with the 400–600 mg dose. The rate of decline of effect averaged 1.5% of the exercise heart rate/hr. Neither resting systolic time intervals nor post‐exercise pulmonary function was affected by this dose range of pamatolol. Based on the latter responses and the isoproterenol dose response curve, we tentatively conclude that pamatolol is relatively cardioselective in man.

A comparative trial of clofibrate and nicotinyl alcohol tartrate in hyperlipoproteinemic patients.

The effects of nicotinyl alcohol tartrate (Roniacol) and clofibrate (Atromid-S) on plasma cholesterol, triglycerides and lipoprotein cholesterol concentrations were compared in 19 patients with hyperlipoproteinemia in a 32-week, double-blind, crossover trial. Determination of serum clofibric acid concentrations, used to check compliance, allowed us to detect an error in the order in which the drugs were dispensed. Both drugs decreased (p <0.01) plasma cholesterol approximately 17% in patients with type II hyperlipoproteinemia. Nicotinyl alcohol reduced plasma triglycerides by 20% in six and clofibrate in eight of the nine patients with type IV hyperlipoproteinemia, although the mean effect, was not statistically significant due to the large variance. Both drugs decreased (p <0.02) very low density lipoprotein (VLDL) cholesterol in the type IV patients; however, clofibrate increased (p <0.05) low density lipoprotein (LDL) cholesterol, whereas nicotinyl alcohol did not. Neither drug altered high density lipoprotein (HDL) levels significantly. In future studies, the effect of hypolipidemic drugs on the major classes of plasma lipoproteins should be determined in addition to the response of plasma lipids.