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Effect of carrier-mediated transport system on intestinal fosfomycin absorption in situ and in vivo.
J Pharmacobiodyn. 1991 Feb; 14(2):82-6.JP

Abstract

Intestinal absorption mechanism of fosfomycin (FOM), a water-soluble and small molecular antibiotic, at the clinical dose level was examined by both in situ single-pass perfusion technique of rat small intestine and oral administration in rat in vivo. Analyzing the luminal concentration-dependence of FOM absorption rates in situ by the equation composed of two terms of carrier transport of Michaelis-Menten type and simple-diffusion, apparent Michaelis constant (Kt), maximal transport velocity (Jmax), and first-order diffusive absorption clearance (Kd) were 1.13 mM, 2.54 nmol/min/cm length, and 0.551 microliters/min/cm length, respectively. At the low FOM concentration in the lumen (0.1 mM), its absorption was reduced to about 60% of the control by inorganic phosphate ion at 1.0 mM in the same manner as the uptake in brush border membrane vesicles of rat small intestine (BBMVs) in vitro. Both the glycol form of FOM at 10 mM, the hydrolyzed metabolite of FOM in the stomach juice, and FOM itself at 10 mM reduced FOM absorption by about 50%, indicating the metabolite to be transported by the same carriers as those of FOM. At the higher FOM concentration (5 mM), its absorption was not reduced by any inhibitor described above. No inhibitory effect of 50 mM phosphate ion on FOM absorption following the oral dosing of 20 mg/kg FOM was found. It was concluded that FOM absorption at the clinical dose (10-20 mg/kg) is barely inhibited by the carrier-mediated system via phosphate transport system observed in the in vitro BBMVs.

Authors+Show Affiliations

Pharmaceutical Research Laboratories, Meiji Seika Kaisha, Ltd., Kanagawa, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

1870077

Citation

Ishizawa, T, et al. "Effect of Carrier-mediated Transport System On Intestinal Fosfomycin Absorption in Situ and in Vivo." Journal of Pharmacobio-dynamics, vol. 14, no. 2, 1991, pp. 82-6.
Ishizawa T, Hayashi M, Awazu S. Effect of carrier-mediated transport system on intestinal fosfomycin absorption in situ and in vivo. J Pharmacobiodyn. 1991;14(2):82-6.
Ishizawa, T., Hayashi, M., & Awazu, S. (1991). Effect of carrier-mediated transport system on intestinal fosfomycin absorption in situ and in vivo. Journal of Pharmacobio-dynamics, 14(2), 82-6.
Ishizawa T, Hayashi M, Awazu S. Effect of Carrier-mediated Transport System On Intestinal Fosfomycin Absorption in Situ and in Vivo. J Pharmacobiodyn. 1991;14(2):82-6. PubMed PMID: 1870077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of carrier-mediated transport system on intestinal fosfomycin absorption in situ and in vivo. AU - Ishizawa,T, AU - Hayashi,M, AU - Awazu,S, PY - 1991/2/1/pubmed PY - 1991/2/1/medline PY - 1991/2/1/entrez SP - 82 EP - 6 JF - Journal of pharmacobio-dynamics JO - J Pharmacobiodyn VL - 14 IS - 2 N2 - Intestinal absorption mechanism of fosfomycin (FOM), a water-soluble and small molecular antibiotic, at the clinical dose level was examined by both in situ single-pass perfusion technique of rat small intestine and oral administration in rat in vivo. Analyzing the luminal concentration-dependence of FOM absorption rates in situ by the equation composed of two terms of carrier transport of Michaelis-Menten type and simple-diffusion, apparent Michaelis constant (Kt), maximal transport velocity (Jmax), and first-order diffusive absorption clearance (Kd) were 1.13 mM, 2.54 nmol/min/cm length, and 0.551 microliters/min/cm length, respectively. At the low FOM concentration in the lumen (0.1 mM), its absorption was reduced to about 60% of the control by inorganic phosphate ion at 1.0 mM in the same manner as the uptake in brush border membrane vesicles of rat small intestine (BBMVs) in vitro. Both the glycol form of FOM at 10 mM, the hydrolyzed metabolite of FOM in the stomach juice, and FOM itself at 10 mM reduced FOM absorption by about 50%, indicating the metabolite to be transported by the same carriers as those of FOM. At the higher FOM concentration (5 mM), its absorption was not reduced by any inhibitor described above. No inhibitory effect of 50 mM phosphate ion on FOM absorption following the oral dosing of 20 mg/kg FOM was found. It was concluded that FOM absorption at the clinical dose (10-20 mg/kg) is barely inhibited by the carrier-mediated system via phosphate transport system observed in the in vitro BBMVs. SN - 0386-846X UR - https://www.unboundmedicine.com/medline/citation/1870077/Effect_of_carrier_mediated_transport_system_on_intestinal_fosfomycin_absorption_in_situ_and_in_vivo_ DB - PRIME DP - Unbound Medicine ER -