TY - JOUR
T1 - Pharmacokinetics of midazolam in mexicans. Evidence for interethnic variability
AU - Chávez-Teyes, Lilia
AU - Castañeda-Hernández, Gilberto
AU - Flores-Murrieta, Francisco Javier
N1 - Funding Information:
The authors wish to thank Mr A. Franco for photographic material. This study was supported by Universidad Juárez Autónoma de Tabasco and Centro de Investigación y de Estudios Avanzados del I.P.N. L. Chávez-Teyes is an Insti-tuto Mexicano del Seguro Social fellow.
PY - 1999
Y1 - 1999
N2 - Objective: To determine midazolam pharmacokinetics in healthy Mexican volunteers and to compare them with the pharmacokinetics reported for other populations. Patients and Methods: Eleven healthy Mexican (mestizo) males received a single midazolam dose intravenously (7.5 mg) and orally (15 mg) with a washout period of at least 7 days. Midazolam plasma concentration was determined by high performance liquid chromatography. Pharmacokinetic parameters were obtained and compared with historical controls reported for other populations. Results: Midazolam pharmacokinetic parameters in Mexicans determined after intravenous administration were (mean ± SEM): clearance 2.54 ± 0.43 ml/min/kg, volume of distribution 0.52 ± 0.1 L/kg and half-life 2.61 ± 0.42 hours. After oral administration the area under the plasma concentration-time curve (AUC) was 941 μg/L·h and the maximum concentration was 271 μg/L. There was a significant correlation between AUC values observed after oral midazolam and clearance (r = -0.71, p < 0.02). Systemic midazolam clearance observed in Mexicans was lower, while oral bioavailability was higher, compared with the values reported in the literature for healthy Caucasian volunteers under similar conditions. Conclusion: Midazolam bioavailability in Mexicans is higher than that reported for Caucasians. This appears to be because of a reduced systemic clearance. Since midazolam is mainly eliminated via biotransformation by CYP3A4, our data suggest the existence of interethnic variations in the activity of this enzymatic system. Increased midazolam bioavailability may lead to an increased incidence of adverse effects. Therefore, administration of midazolam should not be blindly extrapolated from one population to another. Midazolam doses in Mexicans should be reduced in relation to those used in Caucasians.
AB - Objective: To determine midazolam pharmacokinetics in healthy Mexican volunteers and to compare them with the pharmacokinetics reported for other populations. Patients and Methods: Eleven healthy Mexican (mestizo) males received a single midazolam dose intravenously (7.5 mg) and orally (15 mg) with a washout period of at least 7 days. Midazolam plasma concentration was determined by high performance liquid chromatography. Pharmacokinetic parameters were obtained and compared with historical controls reported for other populations. Results: Midazolam pharmacokinetic parameters in Mexicans determined after intravenous administration were (mean ± SEM): clearance 2.54 ± 0.43 ml/min/kg, volume of distribution 0.52 ± 0.1 L/kg and half-life 2.61 ± 0.42 hours. After oral administration the area under the plasma concentration-time curve (AUC) was 941 μg/L·h and the maximum concentration was 271 μg/L. There was a significant correlation between AUC values observed after oral midazolam and clearance (r = -0.71, p < 0.02). Systemic midazolam clearance observed in Mexicans was lower, while oral bioavailability was higher, compared with the values reported in the literature for healthy Caucasian volunteers under similar conditions. Conclusion: Midazolam bioavailability in Mexicans is higher than that reported for Caucasians. This appears to be because of a reduced systemic clearance. Since midazolam is mainly eliminated via biotransformation by CYP3A4, our data suggest the existence of interethnic variations in the activity of this enzymatic system. Increased midazolam bioavailability may lead to an increased incidence of adverse effects. Therefore, administration of midazolam should not be blindly extrapolated from one population to another. Midazolam doses in Mexicans should be reduced in relation to those used in Caucasians.
UR - http://www.scopus.com/inward/record.url?scp=0033046516&partnerID=8YFLogxK
U2 - 10.2165/00044011-199917030-00008
DO - 10.2165/00044011-199917030-00008
M3 - Artículo
SN - 1173-2563
VL - 17
SP - 233
EP - 239
JO - Clinical Drug Investigation
JF - Clinical Drug Investigation
IS - 3
ER -