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Biomedical subjects

D L Azarnoff

Publications and source records attributed to D L Azarnoff.

At least 127 records · Page 7Linked to original sources
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Disposition kinetics of disopyramide in patients with renal insufficiency.

The pharmacokinetics of an intravenous injection of disopyramide was studied in five normal subjects and six patients with varying degrees of renal impairment. The elimination rate constant (beta) was related to the endogenous creatinine clearance (Clcr). However, a decrease in beta was not observed until the Clcr was reduced below 40 ml min-1. Below 40 ml min-1 a linear relationship existed between beta and Clcr. Similarly, the plasma elimination half-life (t 1/2 beta) showed a significant increase when the Clcr was less than 30 ml min-1. Hence, dosage modification for disopyramide is necessary only when renal function is severely impaired. Overall, the apparent volume of distribution in patients with renal insufficiency was reduced to two-thirds of that in normal subjects. Therefore, in patients with Clcr less than 40 ml min-1 both the loading and maintenance dose of disopyramide should be reduced.

Arrhythmias, Cardiac↗
PubMedDate not supplied

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.

ABO Blood-Group System↗
PubMedDate not supplied

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 less than 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 less than 0.02) very low density lipoprotein (VLDL) cholesterol in the type IV patients; however, clofibrate increased (p less than 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.

Adult↗
PubMedDate not supplied

The effects of urine pH and plasma protein binding on the renal clearance of disopyramide.

To ascertain whether the renal clearance of disopyramide (pKa = 8.36) is affected by urine pH, the disposition kinetics of disopyramide were compared during excretion of acidic and alkaline urine following both single dose intravenous (2mg/kg) and oral (5 mg/kg) administration to 4 healthy male volunteers. No significant difference was observed in the plasma concentration-time curve of disopyramide. The mean 72 hour recovery of disopyramide and its N-deisopropyl metabolite (MND) in urine was 55.1 and 20.3% of the dose respectively, with no apparent difference between the two routes of administration or pH of urine. Renal clearance of disopyramide was found to vary with time, which is partly the result of a concentration dependent change in plasma protein binding. The unbound fraction of drug in plasma varied from 0.32 to 0.72 between 0.4 to 4microgram/ml concentration. However, time-dependent change in renal clearance of disopyramide persists even after correction for plasma protein binding.

Administration, Oral↗
PubMedDate not supplied

Induction of salicyluric acid formation in rheumatoid arthritis patients treated with salicylates.

Average steady-state serum salicylate concentrations and salicyluric acid (SU) formation rates were measured in 4 subjects with rheumatoid arthritis. After a salicylate washout period (1 month), the mean observed maximum formation rate of SU was determined by collecting frequent urine samples after a single oral dose of salicylate (35 mg/kg). The patients were then commenced on appropriate high dose salicylate therapy. Two and 5 weeks later, the mean observed maximum rates of SU formation were re-determined along with the average steady-state serum salicylate concentrations. Mean observed maximum SU excretion rates increased significantly between the single-dose study (0.96 +/- 0.22 mg/kg/h) and the last dose of the high dose therapy at 2 weeks (1.65 +/- 0.30 mg/kg/h; p less than 0.01); however, there was no further increase at week 5. Similar increases in the theoretical maximum rate of SU formation (Vmax) were observed between the single-dose study and after 2 weeks of high dose salicylate therapy. Average steady-state serum salicylate concentrations showed no decline between weeks 2 and 5. High dose salicylate therapy leads to acceleration of the rate of SU formation in patients with rheumatoid arthritis and this occurs largely during the first 2 weeks of therapy.

Arthritis, Rheumatoid↗