LJ Van Obbergh, A Robert, F Veyckemans, F Roelants, RK Verbeeck.
Dpt Of Anaesthesiology And Pharmacokinetics Université De Louvain Medical School. 1200 Brussels Belgium
Ropivacaine (R) is a new local anaesthetic agent. This drug is injected in the epidural space (extravascular injection) of children undergoing lower abdominal surgery to provide pain relief. As its pharmacokinetics has not yet been fully studied undertook this study.
METHODS: After Ethics Committee approval and parental informed consent, 35 children (Age 1day to 48 months; Weight 2.8 to 18 Kg median 13.3 Kg) were studied. Under general anaesthesia, a caudal injection of 2 mg/kg plain R was performed. Venous blood samples were drawn for determination of plasma R concentration by HPLC. Four to 9 blood samples were taken, at least three were drawn randomly during the first 60 minutes after injection, as this is the time were Tmax should occur, the others being drawn at various time up to the 12th hour. Population kinetic was then determined with NONMEM (Version V). A one compartment linear model with first order absorption (ADVAN2) was found to fit to our data. Subroutine TRANS 2 was used to calculate the following pharmacokinetic parameters (PK) : Clearance (CL), Volume of distribution (V), Absorption rate (Ka) and lagtime (Alag). PK were estimated using an exponential interpatient error model and an additive intrapatient error model . The introduction of covariates (Age and Weight (WT)) was made after visual inspection of the WRES vs. the covariate and kept when decrease of the objective function of 6 (p~0.01) was observed.
RESULTS: Introducing WT in the model modified significantly the estimations of both the CL and the V however age had no effect. None of these two covariates influenced the Ka or the Alag.
Results of the final selected model :
CL(ml/min) = THETA1* WT/13.3 V (ml) = THETA2* WT/13.3
Ka = THETA3 Alag (min)=THETA4
| THETA | VALUES | Interpatient variability (CV%) | |
| 1 | 101 | CL | 51% |
| 2 | 34300 | V | 41% |
| 3 | 0.0482 | Ka | 51% |
| 4 | 0.97 | Alag | 4% |
CONCLUSIONS:
We have described the pharamcokinetic parameters of R in infants and children and provides the relationships between these parameters and weight. However as the variability remains wide, more studies are required to determine the cause of these variations.
Reference: PAGE 9 () Abstr 129 [www.page-meeting.org/?abstract=129]
Poster: poster