通过饮食磷限制提高膦甲酸的生物利用度。

Enhanced bioavailability of phosphonoformic acid by dietary phosphorus restriction.

作者信息

Loghman-Adham M, Motock G T, Levi M

机构信息

Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132.

出版信息

Biochem Pharmacol. 1994 Oct 7;48(7):1455-8. doi: 10.1016/0006-2952(94)90570-3.

DOI:10.1016/0006-2952(94)90570-3

PMID:7945445

Abstract

Phosphonoformic acid (PFA, foscarnet) is a potent inhibitor of Na(+)-P(i) cotransport in intestinal and renal brush border membranes (BBM). We have studied the effect of dietary phosphorus restriction on intestinal PFA absorption and bioavailability. Rats were placed on low (0.04% P(i), LPD) or normal (0.95% P(i), NPD) phosphorus diets for 5 days, followed by administration of an oral bolus of [14C]PFA (100 mg/kg). Of the oral PFA dose, 60 +/- 4% was absorbed in LPD rats, compared with 43 +/- 3% in NPD rats (P < 0.05, N = 5). This was associated with higher plasma PFA concentrations in LPD compared with NPD rats (44.2 +/- 2.0 and 17.9 +/- 4.3 micrograms/mL, respectively). [14C]PFA uptake, determined in intestinal BBM vesicles (BBMV), was Na+ gradient (Na+out > Na+in) dependent. Dietary phosphorus restriction resulted in a 39.8% increase in the initial (1 min) Na(+)-dependent [14C]PFA uptake by intestinal BBMV. We conclude that PFA absorption is enhanced by dietary phosphorus restriction.

摘要

膦甲酸（PFA，膦甲酸钠）是肠道和肾刷状缘膜（BBM）中Na⁺-无机磷酸盐共转运的有效抑制剂。我们研究了饮食磷限制对肠道PFA吸收和生物利用度的影响。将大鼠置于低磷（0.04%无机磷酸盐，低磷饮食）或正常磷（0.95%无机磷酸盐，正常磷饮食）饮食中5天，然后口服给予一剂[¹⁴C]PFA（100 mg/kg）。口服的PFA剂量中，低磷饮食大鼠吸收了60±4%，而正常磷饮食大鼠吸收了43±3%（P<0.05，N=5）。这与低磷饮食大鼠相比正常磷饮食大鼠血浆PFA浓度更高有关（分别为44.2±2.0和17.9±4.3微克/毫升）。在肠道BBM囊泡（BBMV）中测定的[¹⁴C]PFA摄取依赖于Na⁺梯度（细胞外Na⁺>细胞内Na⁺）。饮食磷限制导致肠道BBMV最初（1分钟）依赖Na⁺的[¹⁴C]PFA摄取增加39.8%。我们得出结论，饮食磷限制可增强PFA的吸收。