Search PubMed⌕ Search

Biomedical subjects

M Mayersohn

Publications and source records attributed to M Mayersohn.

133 records · Page 8Linked to original sources
PubMedDate not supplied

Disposition kinetics of amphotericin B in rats. The influence of dose.

Amphotericin B (Am-B), an antifungal drug, has been used for the treatment of most disseminated fungal infections. The current therapeutic regimens for this drug are complex, at least in part as a result of limited pharmacokinetic information. In this study, we examined the disposition of Am-B as a function of dose in rats. Groups of male Sprague-Dawley rats were given Am-B by a 15-min iv infusion at three different doses. We observed no significant differences in systemic clearance among the Am-B doses studied (4.29 +/- 1.42, 3.83 +/- 0.29, and 3.92 +/- 0.68 ml/min.kg for doses of 0.28, 0.45, and 0.84 mg/kg, respectively). Similarly, small differences were seen in volumes of distribution as a function of dose. We conclude that the disposition kinetics of Am-B were linear over the dose range studied.

Amphotericin B↗
PubMedDate not supplied

Potential error in the measurement of tissue to blood distribution coefficients in physiological pharmacokinetic modeling. Residual tissue blood. I. Theoretical considerations.

Physiological pharmacokinetic models require the determination of tissue to blood distribution coefficients. A theoretical model has been developed and the resulting equations indicate that under certain conditions it is necessary to correct for the presence of drug in the residual blood remaining in the tissue. The potential error in ignoring this residual blood is expressed mathematically in terms of several important factors that include the anatomical features of the tissue (volume fractions of the blood, interstitial fluid, and cellular space) as well as the physicochemical properties of the drug (extent of binding in the blood and tissues). These theoretical considerations and resulting simulations have been applied to experimental literature data for several compounds (methotrexate, digoxin, and biperiden). We conclude that correction for the residual blood is necessary when the values of tissue to blood distribution coefficients are very small or large (relative to one) and when the volume fraction of the blood in tissue is substantial.

Animals↗
PubMedDate not supplied

Potential error in the measurement of tissue to blood distribution coefficients in physiological pharmacokinetic modeling. Residual tissue blood. II. Distribution of phencyclidine in the rat.

A model for predicting the magnitude of error (% Err) in measuring tissue concentrations of a compound that have not been corrected for residual blood in the tissue was previously developed. The model was tested using data for phencyclidine tissue distribution in the rat. It is shown that % Err may be expressed as a function of volume fraction of blood in tissue (VF)B and tissue-to-blood distribution coefficient. Correction for residual blood is important when the volume fraction of the blood in the tissue is large and when the compound is not taken up substantially by the tissue. On the other hand, a correction may not be necessary when (VF)B is small and uptake of the compound into the tissue is substantial.

Animals↗
PubMedDate not supplied

Phencyclidine-specific Fab fragments alter phencyclidine disposition in dogs.

High affinity antibodies (K0 = 3 X 10(9) M-1) against the widely abused drug phencyclidine (PCP) were produced in goats and then purified and extensively characterized for use in in vivo pharmacokinetic studies. An iv dose of 3H-PCP was administered to three dogs, followed 2 hr later by an equimolar dose of PCP-specific antigen-binding fragments (Fab). Within 10 min after Fab administration, the concentration of PCP in the serum had increased 17-56-fold in the three dogs. The Fab administration also produced a 10-fold decrease in volume of distribution and in systemic and renal clearances. The concentration of PCP metabolites decreased for a period of time after Fab administration. Equilibrium dialysis studies showed that the percentage of unbound PCP changed from about 50% before Fab administration to less than 1% unbound after Fab. In addition, the blood/plasma ratio of PCP changed from a near-equal distribution between red blood cells and plasma before Fab to virtually all of the drug being confined to the plasma fraction after Fab administration. Although Fab produced a dramatic redistribution and extensive protein binding of PCP, the route of elimination of PCP was not altered. These data suggest that high affinity anti-PCP Fab could reverse the toxicity of PCP.

Animals↗
PubMedDate not supplied

Toxicokinetics of sulfasalazine (salicylazosulfapyridine) and its metabolites in B6C3F1 mice.

The toxicokinetics of salicylazosulfapyridine (SASP) and its metabolites were investigated in male and female B6C3F1 mice either following single intravenous (5 mg/kg) or oral (67.5, 675, 1350, and 2700 mg/kg) doses, or following three consecutive daily oral doses (675, 1350, and 2700 mg/kg). Plasma concentrations of SASP and its metabolites were quantified by HPLC. Upon intravenous administration, SASP rapidly disappeared from blood with a mean residence time of 0.45-0.78 hr. The only metabolite of SASP found in plasma after an intravenous dose was sulfapyridine (SP). In both sexes, the absolute oral bioavailability of SASP ranged between 16.6-18.2% at a dose of 67.5 mg/kg, and between 2.6-8.7% at doses of 675-2700 mg/kg. Following oral administration of SASP, both SP and AcSP were identified in plasma. The area under the plasma concentration-time curves (AUC) of SP at all four oral doses were approximately 21- to 32-fold or 5- to 25-fold greater than those of SASP in male or female mice, respectively. The acetylated form of SP and AcSP, produced AUC values higher than SASP but much less than SP. Multiple oral doses with SASP did not alter the temporal patterns of SASP absorption and elimination in comparison to a single dose. However, SP accumulated in both sexes following multiple oral doses. A gender-dependent difference in toxicokinetic profiles for SASP and SP was also observed. Female mice displayed a higher Cmax of SASP and SP than did male mice. Although the volume of distribution of SASP was similar in both sexes, the systemic clearance of SASP in males was about twice that observed in females.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMedDate not supplied

Disposition kinetics of d- and l-amphetamine following intravenous administration of racemic amphetamine to rats.

Amphetamine (AP), a chiral drug, displays stereoselective differences in biological action. The effect of stereochemistry on the disposition kinetics of the enantiomers has not been thoroughly studied. We examined the disposition kinetics of AP in rats using a sensitive precolumn derivatization HPLC method that can separate the enantiomers of AP and its metabolites. Male Sprague-Dawley rats were given a short intravenous infusion of racemic AP (15 mg/kg). The systemic and renal clearances, steady-state volume of distribution, and terminal half-life for l-AP were (mean +/- SD), respectively: 65.6 +/- 9.25 ml/min.kg; 15.4 +/- 2.55 ml/min.kg; 4.33 +/- 0.71 liters/kg; and 0.96 +/- 0.13 hr. The corresponding values for d-AP were: 50.8 +/- 6.88 ml/min.kg; 12.5 +/- 2.02 ml/min.kg; 3.84 +/- 0.55 liters/kg; and 1.12 +/- 0.09 hr. There are statistically significant differences between the enantiomers in all pharmacokinetic parameters except half-life. About 40% of the l-AP dose was excreted in urine as l-p-hydroxyamphetamine and 24% as intact drug. The corresponding values for d-AP were 32% and 26%, respectively. p-Hydroxyamphetamine was primarily excreted into urine as the conjugated form. These data indicate stereoselective differences in the pharmacokinetics of the enantiomers of AP after administration of racemic drug in the rat.

Amphetamine↗