The effect of general anesthesia on the intestinal lymphatic transport of lipophilic drugs: comparison between anesthetized and freely moving conscious rat models.
The purpose of this study was to evaluate the impact of general anesthesia on the lymphatic transport of orally administered drugs. Vitamin D(3) (0.5 mg/kg), a model lipophilic molecule with significant lymphatic transport, was administered to anesthetized rats in close proximity to the lymphatic cannulation procedure. The lymphatic and non-lymphatic absorption of the vitamin in this experimental model was compared to lymph-duct cannulated freely moving conscious rats. The amounts of vitamin D(3) transported via the lymph in the anesthetized animals throughout the time frame of this experimental model (8 h) were 25% lower as compared to the conscious animals, but showed similar absorption kinetics. However, the duration of the anesthesia is limited and thus failed to produce the complete picture of the absorption process. The cumulative percent of the vitamin dose that was recovered in the lymph as well as the vitamin plasma AUC values were both 25% lower in the anesthetized animals as compared to the conscious animals. Hence, the anesthesia did not influence the proportion of the vitamin fraction absorbed via the different pathways. The lymph flow rate was significantly decreased by the anesthesia (threefold), however, higher lymph vitamin concentrations in these animals led to lower differences in the vitamin lymphatic transport (25%) between the models. In conclusion, the anesthetized rat model is suitable for approximating the lymphatic transport. However, the conscious rat model is still required in order to have a more precise and complete measurement of lymphatic transport.
Dahan
Arik
A
Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Mendelman
Avivit
A
Amsili
Sofia
S
Ezov
Nathan
N
Hoffman
Amnon
A
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000768:Anesthesia, General; D000778:Anesthetics, Dissociative / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002762:Cholecalciferol / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D003243:Consciousness / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000601:surgery; D007441:Intubation, Gastrointestinal; D007649:Ketamine / Q000494:pharmacology; D008208:Lymphatic System / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014991:Xylazine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000778:Anesthetics, Dissociative; D002762:Cholecalciferol; D014991:Xylazine; D007649:Ketamine