期刊
RENAL FAILURE
卷 25, 期 4, 页码 525-534出版社
TAYLOR & FRANCIS LTD
DOI: 10.1081/JDI-120022543
关键词
pectin; chloroquine; malaria; renal function
The aim of the present study was to investigate the suitability of amidated pectin matrix patch for transdermal chloroquine delivery in an effort to mask the bitter taste when orally administered. Chloroquine has easily measurable outputs that are linked to increased renal Na+ excretion. We thus monitored urinary Na+ output in separate groups intravenously administered chloroquine or topically applied pectin hydrogel chloroquine matrix patch. Male groups of anesthetized Sprague-Dawley rats were placed on a continuous jugular infusion of 0.077 M NaCl at 150 muL min(-1). After 3 h equilibration period, consecutive 20 min urine collections were made over the subsequent 4 h of 1 h control, 1 h 20 min treatment, and 1 h 40min recovery periods for measurements of urine flow and Na+ and K+ excretion rates. The effects of intravenous chloroquine infusion or topical application of pectin hydrogel chloroquine matrix patch were examined in rats in which the drug was added to the infusate or patch applied onto the shaved area during the 1 h 20 min treatment period. The animals were switched back to the infusate alone for the final 1 h 40 min recovery period. Vehicle infused animals acted as controls. Trunk blood was collected after the treatment period from parallel groups for chloroquine measurements. The plasma chloroquine concentrations following iv chloroquine or application of pectin chloroquine hydrogel matrix patch were 9.3+/-0.8 mg L-1 and 7.3+/-1.1 mg L-1, respectively (n=7 in both groups). Chloroquine infusion and pectin chloroquine patch significantly (p<0.01) increased Na+ excretion to peak values of 14.1 +/- 0.9 mu mol min(-1), and 20.35 +/- 1.0 mu mol min(-1), respectively by comparison with controls (9.1 +/- 0.9 mu mol min(-1)), at the corresponding period. The results suggest that the pectin chloroquine patch matrix preparation has potential applications for transdermal delivery of chloroquine and perhaps in the management of malaria.
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