Effect of palmitoyl-DL-carnitine on the 3H-dihydroergotoxine intestinal absorption in rat.
Using the methods of rat intestine perfusion in situ and kinetics examination in vivo, absorption of 3H-dihydroergotoxine (3HDHE) from the gastrointestinal tract into systemic blood was investigated. The aim of the study was to increase absorption of the ergot alkaloid with palmitoyl-DL-carnitine (5 mg/rat). Low absorption of 3HDHE was demonstrated in contrast to fast and almost complete absorption of the model drug theophylline (5 mg kg-1). In the experiment this was evidenced by in situ continuous measurement of the administered activity (125 micrograms kg-1) into a reservoir. At the end of the experiment (120 min) the plasma activity reached 0.034 +/- 0.014%, retention in the intestine achieved more than 60%, uptake in the brain 0.044 +/- 0.015%, cumulative excretion in bile 1.50 +/- 0.31% of administered activity. Palmitoyl-DL-carnitine did not influenced the percentage of activity in the plasma and did not affect bile excretion, retention in the intestine and uptake in the brain. In the vivo experiment oral administration of 3HDHE into the stomach (222 micrograms kg-1) increased activity in plasma (0.069 +/- 0.020% within 24 h), cumulative excretion in urine was 6.1 +/- 3.6%, retention of the drug in the stomach and intestine 46 +/- 12%, activity of the brain 0.11 +/- 0.02%, in the kidney 0.39 +/- 0.17%, and in the liver 0.80 +/- 0.30%. After palmitoyl-DL-carnitine administration the activity of plasma reached 0.084 +/- 0.022% (NS), retention in gastrointestinal tract 39 +/- 9% (NS), activity in the liver 0.71 +/- 0.17% (NS), and activity in the kidney 0.42 +/- 0.13% (NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Martínková
J
J
Department of Pharmacology, Faculty of Medicine, Charles University, Hradec Králové, CSSR.
Tilser
I
I
Krejcí
V
V
Parízek
J
J
Volenec
K
K
D000818:Animals; D001646:Bile / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives*; D002851:Chromatography, High Pressure Liquid; D004088:Dihydroergotoxine / Q000493:pharmacokinetics*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects; D013806:Theophylline / Q000097:blood
D004088:Dihydroergotoxine; D010172:Palmitoylcarnitine; D013806:Theophylline; D002331:Carnitine