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A preliminary study attempting to predict the intrinsic absolute bioavailability of a group of antibacterial 6-fluoroquinolones—including true and imperfect homologues as well as heterologues—was carried out. The intrinsic absolute bioavailability of the test compounds, F, was assessed on permanently cannulated conscious rats by comparing the trapezoidal normalized areas under the plasma concentration–time curves obtained by intravenous and oral routes (n = 8–12). The high-performance liquid chromatography analytical methods used for plasma samples are described. Prediction of the absolute bioavailability of the compounds was based on their intrinsic rat gut in situ absorption rate constant, ka. The working equation was: where T represents the mean absorbing time. A T value of 0.93 (±0.06) h provides the best correlation between predicted and experimentally obtained bioavailabilities (F' and F, respectively) when ka values are used (slope a = 1.10; intercept b = −0.05; r = 0.991). The ka values can also be expressed in function of the in vitro partition coefficients, P, between n-octanol and a phosphate buffer. In this case, theoretical ka values can be determined with the parameters of a standard ka/P correlation previously established for a group of model compounds. When P values are taken instead of ka values, reliable bioavailability predictions can also be made. These and other relevant features of the method are discussed. © 2000 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 1395–1403, 2000

A preliminary study attempting to predict the intrinsic absolute bioavailability of a group of antibacterial 6‐fluoroquinolones—including true and imperfect homologues as well as heterologues—was carried out. The intrinsic absolute bioavailability of the test compounds, F, was assessed on permanently cannulated conscious rats by comparing the trapezoidal normalized areas under the plasma concentration–time curves obtained by intravenous and oral routes (n= 8–12). The high‐performance liquid chromatography analytical methods used for plasma samples are described. Prediction of the absolute bioavailability of the compounds was based on their intrinsic rat gut in situabsorption rate constant, ka. The working equation was:where Trepresents the mean absorbing time. A Tvalue of 0.93 (±0.06) h provides the best correlation between predicted and experimentally obtained bioavailabilities (F′ and F, respectively) when kavalues are used (slope a= 1.10; intercept b= −0.05; r= 0.991). The kavalues can also be expressed in function of the in vitropartition coefficients, P, between n‐octanol and a phosphate buffer. In this case, theoretical kavalues can be determined with the parameters of a standard ka/Pcorrelation previously established for a group of model compounds. When Pvalues are taken instead of kavalues, reliable bioavailability predictions can also be made. These and other relevant features of the method are discussed. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 1395–1403, 2000