Pharmacodynamics and Pharmacokinetics of Levobupivacaine Used for Epidural Anesthesia in Patients with Liver Dysfunction.
The objective of this study was to study the pharmacodynamics and pharmacokinetics of levobupivacaine used for epidural anesthesia in patients with liver dysfunction. Twenty patients aged 20-60, American Society of Anesthesiologists (ASA) graded I-III according to the ASA guidelines, scheduled for elective upper abdominal surgery, were included in the study. They were divided into two groups of ten each. In group I, the patients with liver dysfunction were included, whereas group II was composed of those with normal liver function. In both groups, anesthesia was induced by general anesthesia combined with epidural block, given by T 8-9 interspace injection of 1.8 mg kg(-1) levobupivacaine (0.75 %) with 5 μg mL(-1) of adrenaline in 1.5 min. The sensory and motor blockade indices were recorded for 30 min after the injection. The plasma concentration of levobupivacaine was determined by high performance liquid chromatography from 0 to 1440 min after the injection and pharmacokinetics of the drug were calculated. The onset and recovery time from the sensory block in the two groups were similar with no significant difference (P > 0.05). The maximum spread of anesthetic effect, the number of spinal segments regressed, onset time, and degree of motor block after the injection were also insignificantly different in the two groups. The plasma levobupivacaine concentration/time curve of the liver dysfunction (group I) was significantly higher than that of the controls (group II). In the liver dysfunction patients, the volume of distribution (V/F) was significantly increased, the elimination rate, i.e., half-life (t 1/2β ), was prolonged, and the elimination rate constants (K 12 and K 10) were significantly decreased (P < 0.05 or P < 0.01). The patients with liver dysfunction injected with 0.75 % levobupivacaine exhibited normal onset and recovery time of the sensory and motor blocks within 30 min. However, in these patients, the metabolism of levobupivacaine was significantly slower as evidenced by the higher blood concentration of the drug than in cases with normal functioning liver.
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Juhong
J
Ran
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Yanping
Y
Wang
The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, Henan, China.
Fangkun
F
Li
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. drweizhang@163.com.
Wei
W
Zhang
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. mminyu@126.com.
Minyu
M
Ma
D000328:Adult; D000767:Anesthesia, Epidural; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D002045:Bupivacaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D000077554:Levobupivacaine; D008107:Liver Diseases / Q000601:surgery*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012677:Sensation / Q000187:drug effects; D013127:Spinal Nerves / Q000187:drug effects; D014018:Tissue Distribution
D000779:Anesthetics, Local; D000077554:Levobupivacaine; D002045:Bupivacaine
Amides; Epidural anesthesia; Liver dysfunction; Pharmacodynamics; Pharmacokinetics