Short-term effects of administration of anticonvulsant drugs on free carnitine and acylcarnitine in mouse serum and tissues.
1. The short-term evolution of concentrations of free carnitine and acylcarnitine was studied in the serum, liver, kidney, heart and skeletal muscle of mice after administration of single therapeutic doses of the anticonvulsant drugs, valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT) and phenobarbitone (PHB). 2. The effects of the drugs were immediate but transitory, control levels of free carnitine and acylcarnitine having been recovered or almost recovered in serum and in all tissues 8 h post administration (p.a.). 3. VPA was the only drug that significantly reduced free carnitine concentration in serum, which recovered control levels by 4 h p.a. 4. All the drugs studied brought about marked deficits of serum acylcarnitine, which had disappeared 2 h p.a. in the case of VPA and not until 8 h p.a. for CBZ, PHT or PHB. 5. The minimum concentrations of free carnitine and acylcarnitine in serum were invariably associated with the maximum concentration of drug in serum. 6. Free carnitine concentration was not affected by VPA in any tissue, PHT and PHB brought about significant deficits in heart and kidney, and CBZ a significant deficit in muscle. 7. Acylcarnitine concentration was significantly reduced in heart, kidney and muscle by CBZ, PHT and PHB, but in liver the effects of all drugs were very small. 8. These results are compatible with the hypothesis that the primary cause of anticonvulsant-induced alteration of carnitine metabolism is interference with renal reabsorption of carnitine.
Camiña
M F
MF
Department of Biochemistry (Faculty of Pharmacy), University of Santiago de Compostela, Spain.
Rozas
I
I
Gómez
M
M
Paz
J M
JM
Alonso
C
C
Rodriguez-Segade
S
S
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D000091402:Prohibitins; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; C000717333:Phb2 protein, mouse; D000091402:Prohibitins; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D002331:Carnitine; D010634:Phenobarbital