Table 4

Drugs with large blood-to-plasma concentration ratios, Kb/p, in humans^4-a

Class of drugs	Drug	Kb/p	Method	Reference
Inotrop/vasodilator	(+) Pimobendan	3.2^4-c	ex vivo	Chu et al. (1995a)
	(−) Pimobendan	4.5^4-c	ex vivo	Chu et al. (1995a)
Immunosuppressivum	Cyclosporin A	4^4-b	in vitro, 20°C	Niederberger et al. (1983)
		2^4-b	in vitro, 37°C	Niederberger et al. (1983)
		4.6^4-b	ex vivo, 20°C	Hamberger et al. (1988)
		2.0^4-b	ex vivo, 37°C	Kurokawa et al. (1996)
	Rapamycin	14.3^4-b	in vitro, 37°C	Yatscoff et al. (1993b)
	Tacrolimus	22.6^4-b	in vitro, 37°C	Beysens et al. (1991)
		29,^4-b 55.5^4-b	ex vivo, 37°C	Jusko et al. (1995)
				Jusko and D’Ambrosio (1991)
Carbonic anhydrase inhibitor	Acetazolamide	2.9^4-b ^, ^4-c	in vitro, 37°C	Wallace and Riegelman (1977)
Diuretic	Dorzolamide	>100^4-b ^, ^4-c	ex vivo	Biollaz et al. (1995)
	Methazolamide	241^4-b ^, ^4-c	ex vivo	Bayne et al. (1981)
Thiazide-like diuretic	Chlorthalidone	30.7^4-b ^, ^4-c	in vitro, 37°C	Fleuren and van Rossum (1977)
		32^4-b ^, ^4-c	ex vivo	Fleuren and van Rossum (1977)
Antimalarial	Chloroquine	3.5, 3.2	in vitro, 20°C	Rambo et al. (1985)
				Nosàl et al. (1988)
	Desethylchloroquine	3.1	in vitro, 20°C	Rambo et al. (1985)
	Desethylamodiaquine	3.1	ex vivo	Winstanley et al. (1987)
Antirheumatic	Hydroxychloroquine	7.2	ex 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.