Interference of heparin in plasma levocarnitine determination with radioenzyme assay.

This paper describes the interference of heparin (CAS 9005-49-6) in whole plasma used for free and total levocarnitine (L-carnitine, CAS 541-15-1) analysis. Alkaline hydrolysis required for total L-carnitine measurement does not overcome the problem. The same interference is also present in long-chain acyl-L-carnitine assay, because heparin precipitates together with proteins and long-chain esters of L-carnitine in the acid insoluble fraction of perchloric acid treated plasma sample.

Plasma concentration, urinary excretion and renal clearance of L-carnitine during pregnancy: a reversible secondary L-carnitine deficiency.

Plasma concentration, urinary excretion and renal clearance of free, total and esterified L-carnitine were monitored monthly in 14 women during the last 6 months of pregnancy and 1 month after delivery. Plasma concentration and renal clearance measured 1 month after delivery overlapped with normal values for females of comparable age, and were considered the reference values for further comparisons. Plasma concentration of free, total and esterified L-carnitine decreased during pregnancy, reaching values as low as half of those measured 1 month after delivery, whereas urinary excretion and renal clearance, mainly of L-carnitine esters, increased, with renal clearance reaching a peak at the 16th week of pregnancy.

Effect of acetyl-L-carnitine treatment on the levels of levocarnitine and its derivatives in streptozotocin-diabetic rats.

The effect of diabetes induced by streptozotocin and that of acetyl-L-carnitine (ALC) hydrochloride (CAS 5080-50-2) treatment on the homeostasis of the levocarnitine (L-carnitine) moiety was investigated in Sprague-Dawley rats. The diabetic status was ascertained by measuring blood glucose. L-carnitine (LC), total acid soluble L-carnitine (TC) and ALC were measured in serum, tissues and urine by radioenzymatic methods.

Hemodynamic and metabolic activities of propionyl-L-carnitine in rats with pressure-overload cardiac hypertrophy.

Evidence has been put forth that a number of human and experimental cardiomyopathies are associated with a lower myocardial carnitine content. This study was performed to test the hypothesis that the correction of carnitine derivative, propionyl-L-carnitine (PLC), may improve cardiac function. Repeated administration of PLC was compared to saline with respect to cardiac function in rats with pressure-overload cardiac hypertrophy and low myocardial carnitine levels.

Pharmacokinetic investigation of ST 789 in rats and mice.

Pharmacokinetics of ST 789 were investigated in rats and mice after oral, intravenous, subcutaneous and intramuscular routes. A HPLC method validated for pharmacokinetic studies allowed the Authors to assay ST 789 concentration in plasma, urine and tissues. ST 789 interacted poorly with albumin and plasma proteins.

Enzymes in stereoselective pharmacokinetics of endogenous substances.

The use of enzymes to assay individual components of the L-carnitine family in pharmaceuticals, foodstuffs, and biological fluids with various forms of detection is reviewed. The most useful enzyme in the assay of compounds of the L-carnitine family is carnitine acetyl transferase (CAT), which catalyses the reversible interconversion of L-carnitine and its short-chain acyl esters. CAT can be used in one or more coupled reactions combined with U.

High-performance liquid chromatographic evaluation of Med 15 and its metabolites Med 5 and tolmetin in rat plasma.

A simple and reliable high-performance liquid chromatographic method is described for the quantitative analysis of the new non-steroidal anti-inflammatory agent Med 15 and its metabolites Med 5 and tolmetin in rat plasma. After selective extraction the three analytes and an internal standard (p-phenyl-phenol) were separated on a reversed-phase Ultrasphere 5 micron column using potassium dihydrogenphosphate (0.05 M)-acetonitrile (52:48) (pH 4.

L-carnitine and carnitine ester transport in the rat small intestine.

L-carnitine and its esters (acetyl-L-carnitine and propionyl-L-carnitine) at pharmacological doses (1, 5 and 10 mM) are absorbed by the rat jejunum by simple diffusion. Partition coefficients of carnitine esters determined in lipophilic media (diethyl ether/water and olive oil/water) are greater than that of L-carnitine. It would therefore seem that esters diffuse more easily through the lipid component of the intestinal barrier.

Protein binding of L-carnitine family components.

L-carnitine and its short-, medium- and long-chain acyl esters constitute the L-carnitine family. These compounds in the body are equilibrated according to a homeostatic equilibrium preserved and, when impaired, restored by a dynamic inter-exchange between L-carnitine and its esters, catalysed by carnitine acyl transferases, and a tubular reabsorption process with differentiated thresholds for each component. The interaction of these compounds with albumin and plasma proteins of rats, dogs and humans was carefully investigated by means of ultrafiltration and gel filtration techniques.

Homeostatic equilibrium of L-carnitine family before and after i.v. administration of propionyl-L-carnitine in humans, dogs and rats.

Propionyl-L-carnitine is a minor component of L-carnitine family which, when exogenously administered, proved to possess interesting cardiovascular activities. In this paper the pharmacokinetics of propionyl-L-carnitine was investigated in humans, dogs and rats after intravenous administration. In all the three species the base homeostatic equilibrium was carefully investigated in plasma and in urine during the 24 h period before the administration.

Chromatographic and non-chromatographic assay of L-carnitine family components.

L-Carnitine and its acyl esters constitute an endogenous pool of the L-carnitine family, involved in the uptake of free fatty acids in the mitochondria by transfer across their membrane of the acyl moieties to fuel the beta-oxidation and the release of the acetyl group from the mitochondria to the cytosol. Therefore acyl-L-carnitine and acyl-L-carnitine transferase are involved in a homeostatic equilibrium with the cells. As most of these substances need to be monitored in foods, chemical and pharmaceutical processes and biological fluids, an overview of the main methods for assaying them is provided here, with specific reference to the intrinsic performance of each analytical procedure and with suggestions on the correct storage and manipulation of analytical samples.

High-performance liquid chromatographic evaluation of PCF 39, a new immunomodulator agent.

An high-performance liquid chromatographic analysis of PCF 39, N2-[5-(hypoxanthin-9-yl)pentyloxycarbonyl]-L-arginine, with ultraviolet detection, has been devised and validated. The main pharmacokinetic results encountered for rats treated intravenously with PCF 39 at a dose of 100 mg/kg are described.

A radiometric assay for ganglioside sialidase applied to the determination of the enzyme subcellular location in cultured human fibroblasts.

A radiometric method for the assay of ganglioside sialidase in cultured human fibroblasts was set up. As substrate, highly radioactive (1.28 Ci/mmol) ganglioside GDla isotopically tritium-labeled at carbon C-3 of the long chain base was employed; the liberated, and TLC separated [3H]GM1 was determined by computer-assisted radiochromatoscanning.

Pyruvate-dehydrogenase complex in ataxic patients: enzyme deficiency in ataxic encephalopathy plus lactic acidosis and normal activity in Friedreich ataxia.

Pyruvate dehydrogenase complex (PDHC) activity was measured in cultured fibroblasts from 12 patients with Friedreich's ataxia (FA), and in 1 patient with lactic acidosis and ataxia. The activities obtained after extraction of PDHC by different methods were compared. Triton-X-100 extraction yielded enzyme activities 5 to 10 times greater than those obtained with the older methods.

Heterogeneity of carnitine-palmitoyltransferase deficiency.

Episodes with muscle ache, rhabdomyolysis and myoglobinuria with or without associated renal insufficiency are characteristic of muscle carnitinepalmitoyltransferase (CPT) deficiency. However, patients differ from each other in many aspects, such as the kind of stimulus that triggers rhabdomyolysis, the ability to produce ketone bodies when fasting, whether the enzyme defect is localized in skeletal muscle or is general, and the nature of the enzyme defect, which may be in CPT I or CPT II or both. Studies of muscle, liver and fibroblasts from a patient with recurrent rhabdomyolysis spontaneously occurring or triggered by exercise or fever, revealed a CPT deficiency in the muscle and liver biopsy samples but normal CPT activity in cultured cells, differing from previously reported patients.