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Biomedical subjects

R P Kershner

Publications and source records attributed to R P Kershner.

8 recordsLinked to original sources
PubMed1996

Relationship of FK506 whole blood concentrations and efficacy and toxicity after liver and kidney transplantation.

FK506 (tacrolimus) is a safe and effective immunosuppressant for the prevention of organ rejection after organ transplantation. FK506 has a relatively narrow therapeutic index and the correlation of dose to blood concentration is poor as a result of moderate variability in pharmacokinetic parameters between patients. Therapeutic monitoring of whole blood FK506 drug concentrations has been used in an effort to determine whether a relationship exists between concentrations of FK506 in the blood and the development of toxicity or the risk for organ rejection. An analysis of the relationship between FK506 blood levels and the occurrence of toxicity and rejection was carried out using data from four recent clinical trials. Trough FK506 levels within a 7-day window before the onset of rejection or toxicity were analyzed using logistic regression models. In kidney transplant patients (n=92), a significant correlation between FK506 levels and the incidence of both toxicity (P=0.01) and rejection (P=0.02) was seen. In liver transplant patients from three clinical trials, FK506 levels correlated well with the incidence of toxicity (P < or = 0.01); however, there was no significant relationship between FK506 levels and the incidence of rejection. It is concluded that therapeutic monitoring of whole blood FK506 levels may be useful for minimizing the risks of both toxicity and rejection in kidney transplant patients and for minimizing the risk of toxicity in liver transplant recipients.

Dose-Response Relationship, Drug↗
PubMed1996

Relationship of whole-blood FK506 concentrations to rejection and toxicity in liver and kidney transplants.

FK506 (tacrolimus) has been shown to be a safe and effective immunosuppressant for the prevention of organ rejection after liver and kidney transplantation. Like cyclosporine, the use of FK506 has been associated with some adverse effects such as toxicity and organ rejection. Therapeutic monitoring of the whole-blood FK506 drug concentrations has been used in an effort to determine how the concentration of FK506 in the blood is related to the development of toxicity or the risk for organ rejection. Cox regression analysis of two recent clinical trials of FK506 in patients receiving kidney and liver transplants shows a significant correlation between the whole-blood FK506 concentrations and the incidence of both toxicity and organ rejection. Because of these relationships and the pharmacokinetics of FK506, therapeutic monitoring of the whole-blood FK506 levels is expected to be helpful for minimizing the risks of both toxicity and rejection in liver and kidney transplants.

Dose-Response Relationship, Drug↗
PubMed1987

Comparison of intravenous milrinone and dobutamine for congestive heart failure secondary to either ischemic or dilated cardiomyopathy.

Milrinone and dobutamine are positive inotropic agents with beneficial hemodynamic effects in patients with congestive heart failure. This study was undertaken to compare the effects of intravenous milrinone and dobutamine in patients with stable New York Heart Association class III or IV congestive heart failure and to test the hypothesis that intravenous milrinone is at least as beneficial as dobutamine in this setting. Seventy-nine patients were randomized to either dobutamine therapy at incremental doses of 2.5, 5, 7.5, 10, 12.5 and 15 micrograms/kg/min, or milrinone as a bolus of 50 or 75 micrograms/kg followed by an infusion of 0.5 to 1.0 micrograms/kg/min. Both agents significantly increased heart rate, cardiac index and stroke volume index and decreased pulmonary artery wedge pressure and systemic vascular resistance compared with baseline levels (p less than 0.01). During sustained infusion for 48 hours, no difference in hemodynamic effects was observed between the 2 drugs. Ventricular tachycardia occurred in 5 patients (3 taking milrinone, 2 taking dobutamine); 1 patient taking milrinone had ventricular fibrillation. Milrinone and dobutamine elicited similar beneficial hemodynamic results with relatively few adverse effects.

Cardiomyopathy, Dilated↗
PubMed1983

Oral bioavailability and intravenous pharmacokinetics of amrinone in humans.

Fourteen healthy males received two 75-mg doses of amrinone as a single capsule and as an intravenous solution in a single-dose crossover study. The mean (+/-SD) bioavailability, based on the area under the plasma concentration versus time curves, was 0.93 +/- 0.12. The plasma data for these subjects during the intravenous phase was described by an open two-compartment body model with a mean (+/-SD) apparent first-order terminal elimination rate constant, beta, of 0.19 +/- 0.06 hr-1, which corresponds to a half-life of 3.6 hr.

Administration, Oral↗
PubMed1983

Dose proportionality of amrinone.

Amrinone was given to 18 healthy subjects in doses of 75, 150, and 225 mg in a randomized crossover design. Plasma levels were shown to rise in proportion to dose. The mean plasma AUC, extrapolated to infinite time, was determined for each dose level; the values obtained were 4, 8.18, and 12.35 micrograms . hr/ml for the 75-, 150-, and 225-mg doses. Mean maximum observed plasma concentrations were 1.03, 1.74, and 2.58 micrograms/ml. At higher doses the extrapolated AUC is more variable, but it is linear over the range of 0.73 to 3.81 mg/kg. The apparent first-order terminal elimination rate is not dose dependent and corresponds to a t1/2 of 3.85 hr.

Adult↗
PubMed1979

Riboflavin nutritional status and absorption in oral contraceptive users and nonusers.

Riboflavin nutritional status, based on erythrocyte glutathione reductase (EGR) determinations, and the absorption of the vitamin after 10-mg oral doses were assessed in a group of oral contraceptive users (group OC, n = 18) and in a group of nonusers (group NOC, n = 17). Before administration of test doses of riboflavin, mean EGR levels of 4.06 (group OC) and 4.44 (group NOC) mumoles glutathione reduced per minute per gram of hemoglobin were not significantly different. After oral administration of riboflavin, a significant increase in EGR levels was observed within each group although no significant differences were detected between groups. Mean EGR levels continued to be slightly lower for group OC compared to group NOC. Oral absorption of riboflavin based on urinary excretion results was not significantly different between the groups. These findings indicate OC use does not significantly affect riboflavin nutritional status in a subject population having adequate nutrition of moderate to high socioeconomic status. Significant reductions in EGR levels which have been previously reported for OC users appear to be associated with a low socioeconomic status.

Absorption↗
PubMed1977

Effect of antacids on absorption of clorazepate.

The effect of a magnesia and alumina antacid suspension on the absorption of clorazepate dipotassium was studied in 15 normal healthy adult subjects who ingested a 15-mg dose of clorazepate alone or with single or multiple doses of antacid. The results of this three-period randomized complete crossover study showed a trend of initially slower absorption and lower peak nordiazepam plasma levels when administered with the antacid suspension. However, there were no significant differences among treatments in the extent of absorption as measured by the area under the plasma level-time curves. Clorazepate plasma levels were of relatively short duration and similar for all treatments. The urinary excretion pattern was likewise comparable with conjugated oxazepam, the major species measured. Plasma elimination half-lives of nordiazepam and clorazepate were not affected by the antacid treatments.

Adult↗