Table 4

Drugs with large blood-to-plasma concentration ratios, Kb/p, in humans4-a

Class of drugsDrugKb/pMethodReference
Inotrop/vasodilator(+) Pimobendan3.24-c ex vivo Chu et al. (1995a)
(−) Pimobendan4.54-c ex vivo Chu et al. (1995a)
ImmunosuppressivumCyclosporin A 44-b in vitro, 20°C Niederberger et al. (1983)
24-b in vitro, 37°C Niederberger et al. (1983)
4.64-b ex vivo, 20°C Hamberger et al. (1988)
2.04-b ex vivo, 37°C Kurokawa et al. (1996)
Rapamycin14.34-b in vitro, 37°C Yatscoff et al. (1993b)
Tacrolimus22.64-b in vitro, 37°C Beysens et al. (1991)
29,4-b 55.54-b ex vivo, 37°C Jusko et al. (1995)
Jusko and D’Ambrosio (1991)
Carbonic anhydrase inhibitorAcetazolamide2.94-b , 4-c in vitro, 37°C Wallace and Riegelman (1977)
DiureticDorzolamide>1004-b , 4-c ex vivo Biollaz et al. (1995)
Methazolamide2414-b , 4-c ex vivo Bayne et al. (1981)
Thiazide-like diureticChlorthalidone30.74-b , 4-c in vitro, 37°C Fleuren and van Rossum (1977)
324-b , 4-c ex vivo Fleuren and van Rossum (1977)
AntimalarialChloroquine3.5, 3.2in vitro, 20°C Rambo et al. (1985)
Nosàl et al. (1988)
Desethylchloroquine3.1in vitro, 20°C Rambo et al. (1985)
Desethylamodiaquine3.1ex vivo Winstanley et al. (1987)
AntirheumaticHydroxychloroquine7.2ex vivo Tett et al. (1988)
  • 4-a In accord with equation (4), the erythrocyte-to-plasma concentration ratios, Ke/p, exceed the corresponding Kb/p values of the listed compounds. Similarly, the red blood cell concentrations exceed the whole blood concentrations for the listed compounds, e.g., if Kb/p = 2.0, then Ke/p = 3.9, and the erythrocyte concentrations are 3.9 times larger than the whole blood concentrations.

  • 4-b Saturable red blood cell partitioning; Kb/p measured at lower end of therapeutic plasma concentration range.

  • 4-c Value estimated from data in reference literature.