Hepatic function as assessed by lidocaine metabolism in sickle cell disease.
OBJECTIVE
To evaluate hepatic drug metabolism, as determined by the formation of monoethylglycinexylidide (MEGX) after lidocaine injection and indocyanine green (ICG) clearance, in patients with sickle cell disease.


METHODS
A case-control study including 19 patients with homozygous hemoglobin S, and 13 age- and sex-matched black control subjects. Serum MEGX concentration was measured after intravenous injection of 1 mg/kg (maximum 50 mg) lidocaine. ICG (0.5 mg/kg) was injected concomitantly and absorbance (805 nm) of serum was measured over time to determine its volume of distribution, serum half-life, and hepatic blood flow.


RESULTS
MEGX formation at 15 minutes was decreased in patients with sickle cell disease compared with formation in the control subjects (39.9 +/- 18.0 vs 65.6 +/- 50.0 micrograms/L, respectively, p < 0.02). The volume of distribution of ICG was increased in patients with sickle cell disease compared with that in the control subjects (0.21 +/- 0.09 vs 0.11 +/- 0.03 L/kg, p < 0.01). This partly accounts for the decreased MEGX formation. The ICG half-life was similar in both groups (3.8 +/- 1.5 vs 3.1 +/- 1.0 min). Hepatic blood flow, derived from ICG clearance, was increased in sickle cell patients compared with that of the control subjects (12.2 +/- 4.5 vs 8.1 +/- 2.1 ml/kg/min, p < 0.01).


CONCLUSIONS
Hepatic drug metabolism, as assessed by MEGX formation after lidocaine injection, is impaired in patients with sickle cell disease. This impairment may have clinical implications when using hepatically metabolized medications in patients with sickle cell disease.
Gremse
D A
DA
Department of Pediatrics, University of South Alabama College of Medicine, Mobile, Alabama 36640-0130, USA.
Fillingim
E
E
Hoff
C J
CJ
Wells
D J
DJ
Boerth
R C
RC
D000328:Adult; D000755:Anemia, Sickle Cell / Q000378:metabolism* / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004396:Coloring Agents; D004395:Dye Dilution Technique; D005260:Female; D006207:Half-Life; D006720:Homozygote; D006801:Humans; D007208:Indocyanine Green; D007223:Infant; D008012:Lidocaine / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008102:Liver Circulation; D008111:Liver Function Tests; D008297:Male; D013997:Time Factors
D004396:Coloring Agents; D008012:Lidocaine; C001173:monoethylglycinexylidide; D007208:Indocyanine Green