Clinical trial NCT02588118: Gender and PK-PD of Propofol and Cisatracurium
Official title: Effect of Gender on the Pharmacokinetics-pharmacodynamics of Propofol and Cisatracurium Besylate
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Gender
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2015-10-27
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: differences between equal numbers of males and females

Brief summary: In recent years it has become clear that gender differences exist both in the pharmacokinetics and the pharmacodynamics of drugs related to the practice of anesthesia. Differences in pharmacokinetics are more straightforward to study than differences in clinical effects. However, isolated pharmacokinetic data are of less value if they are not accompanied by measurements of clinical effects. Males are more sensitive than females to propofol. It may therefore be necessary to decrease the propofol dose by 30-40% in males. Females have 20-30% greater sensitivity to the muscle relaxant effects.

Detailed description: Background: In recent years it has become clear that gender differences exist both in the pharmacokinetics and the pharmacodynamics of drugs related to the practice of anesthesia. Differences in pharmacokinetics are more straightforward to study than differences in clinical effects. However, isolated pharmacokinetic data are of less value if they are not accompanied by measurements of clinical effects. Males are more sensitive than females to propofol. It may therefore be necessary to decrease the propofol dose by 30-40% in males. Females have 20-30% greater sensitivity to the muscle relaxant effects.

Methods: Anaesthesia is induced with propofol 2 mg/kg (t0) followed by cisatracurium 0.1 mg/kg 1 min from propofol administration (t2). Patients will be monitored using the conventionally available bispectral index monitoring for propofol concentrations and Relaxometer mechanomyograph neuromuscular monitoring for cisatracurium. Serial arterial blood samples (5 ml) were withdrawn in EDTA-tubes before cisatracurium administration, 1, 3, 5, 7, 10, 13, 16, 19, 22, 25, 30, 60 and 90 min following administration. Blood samples were assayed in duplicate using high performance liquid chromatograph. Pharmacokinetic analysis was performed by fitting the cisatracurium blood concentration time profile of individual patients, to non-compartmental as well as multi-compartmental pharmacokinetic models.

Eligibility criteria: Inclusion Criteria:

1. either males or females

Exclusion Criteria:

1. Liver disease

Primary outcomes:
measure: propofol elimination half life
timeFrame: before administration till 120 minutes
Secondary outcomes:
measure: cisatracurium elimination half life
timeFrame: before administration till 120 minutes
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
city: Xi'an
country: China
facility: Xijing hospital of Fourth Military Medical University
state: Shaanxi
Study officials:
affiliation: Medical University of Graz
name: Ashraf Dahaba
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schmith VD, Fiedler-Kelly J, Phillips L, Grasela TH Jr. Prospective use of population pharmacokinetics/pharmacodynamics in the development of cisatracurium. Pharm Res. 1997 Jan;14(1):91-7. doi: 10.1023/a:1012015719694.
citation: Vuyk J, Oostwouder CJ, Vletter AA, Burm AG, Bovill JG. Gender differences in the pharmacokinetics of propofol in elderly patients during and after continuous infusion. Br J Anaesth. 2001 Feb;86(2):183-8. doi: 10.1093/bja/86.2.183.