Differential kinetic profiles and metabolism of primaquine enantiomers by human hepatocytes

Malaria Journal

Table 1 The intrinsic clearance of PQ and its enantiomers in human hepatocytes

	(±)-PQ	(+)-PQ	(−)-PQ
Time interval (min) for calculation of elimination rate constant	0–60	0–60	0–60
λ (h⁻¹)^a	0.34	0.19	0.64
t½ (h)^b	2.03	3.62	1.09
t½ (min)	121.8	217	65
CLint in vitro [(mL/h)/million cells^c]	0.273	0.153	0.509
CLint in vitro [(µL/min)/million cells]	4.55	2.55	8.49
CLint in vivo [(L/h)/kg body mass]^d	0.69	0.39	1.30
CLint in vivo [(mL/min)/kg body mass]	11.58	6.49	21.60
CL_h,b [(L/h)/kg body mass]^e	0.45	0.30	0.63
CL_h,b [(mL/min)/kg body mass]	7	5	11
CLh,b (% hepatic blood flow)^f	36	24	51

λ elimination rate constant, Clint intrinsic clearance, CL _h,b hepatic blood clearance
^aλ is taken as the -slope of the linear portion of the log-linear regression (0-60 min)
^bHalf-lives computed from \({\lambda}({\text{t1}}/2 = {\text{ln}}(2)/\lambda\)
^c \(({\text{ln2/T1/2}})/{\text{mio viable cells}} \times 1000\)
^d \(( {\text{CLint}} /1000) * ({\text{cells/g/liver}})* ({\text{g liver / kg body weight}})\). Hepatocellularity is given as 99 million cells/g liver; average human liver weight is 25.7 g/kg body mass
^e \({\text{CLh}} = ( {\text{Qh}} * {\text{CLint}},{\text{scaled}})/ ( {\text{Qh}} + {\text{CLint}},{\text{scaled}})\) Qh hepatic blood flow (well-stirred liver model) is given as 20.7 (mL/min)/kg body mass
^fQh (mL/min/kg body weight): 55 (rat); 30.9 (dog); 43.6 (monkey); 20.7 (human)

ISSN: 1475-2875