RT Journal Article
SR Electronic
T1 Lymphatic distribution of 3'-azido-3'-deoxythymidine and 3'-azido-2',3'-dideoxyuridine in mice.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 655
OP 658
VO 23
IS 6
A1 K K Manouilov
A1 C A White
A1 F D Boudinot
A1 I I Fedorov
A1 C K Chu
YR 1995
UL http://dmd.aspetjournals.org/content/23/6/655.abstract
AB Recently, it was shown that human immunodeficiency virus (HIV)-infected cells preferentially locate in lymphoid tissue early in the course of infection. Therefore, it is important to characterize the disposition of the anti-HIV agents, 3'-azido-3'-deoxythymidine (AZT) and 3'-azido-2', 3'-dideoxyuridine (AZdU), in the lymphatic system. The disposition of AZT and AZdU in serum and neck, axillary, and mesenteric lymph nodes was studied in mice after intravenous, oral, and intraperitoneal administrations of 50 mg/kg doses. Samples were collected at 0.08, 0.5, 1, 2, 3, 4, and 6 hr after dosing and nucleoside concentrations were determined by HPLC. Pharmacokinetic parameters were estimated using noncompartmental analysis. Maximum concentration, half-life, and area under the serum concentration vs. time curve (AUC) obtained from the serum concentration data were similar for both compounds after intravenous and intraperitoneal administrations; however, a difference in oral bioavailability for AZT and AZdU (49% and 76%, respectively) was noted. Patterns of regional distribution in lymph nodes were similar for both drugs; however, the accumulation of AZdU in the various lymph nodes, according to AUC values, was 3-76% greater than that for AZT. The relative exposure re = AUClymph/AUCserum) of both nucleosides exhibited a dependence on route of administration. Intravenous and oral administrations resulted in a greater distribution of nucleoside into axillary lymph nodes, compared with neck and mesenteric lymph nodes. Following intraperitoneal administration, however, distribution was similar in all three regions. AZT and AZdU distribute into the lymphatic system; however, AZdU accumulation was greater than that of AZT.(ABSTRACT TRUNCATED AT 250 WORDS)