Pharmacokinetics And Pharmacodynamics Of Ropivacaine During Epidural Anesthesia In Renal Function Failure

Objective :This trial was designed to investigate the profile of the pharmacokinetics and pharmacodynamics of ropivacaine during epidural anesthesia in the patient with renal function failure.Methods:The 8 patients with renal function failure and the 8 volunteers with normal renal function received 1.6mg/kg ropivacaine hydrochloride (7. 5mg/ml) epidurally . Peripheral arterial and venous plasma samples were collected. The plasma concentrations of ropivacaine were measured using high-performance liquid chromatographiy . Assessments of sensory and motor block were made.Results :The plasma concentration-time curves of ropivacaine was fitted to a two-compartment open model . The major arterial and venous pharmacokinetics parameters in the patients with renal function failure were as followed: Ka=0.24±0.15 and 0.17±0.14 (1/min), t1/2β=173. 81±41. 14 and 182. 79±9.08 (min), AUC=453. 36 ±320. 67 and 460. 99±274. 59 ( (mg/L)min), CL=0. 4±0. 28 and 0. 37±0. 26 (mg/min/(mg/L)), Tpeak=13.71±5.31 and 20. 72±10. 79(min), Cmax=2. 09±1. 13 and 1. 81±1.04(mg/L) respectively. The major arterial and venous pharmacokinetics parameters in the volunteers with normal renal function were as followed Ka=0. 22±0. 12 and 0.41±0.45 (1/min), t1/2 β =120. 14±34. 79 and 108.37±40.09 (min), AUC=331.98±103.19 and 337. 91±257. 28 ((mg/L)min ), CL=0.44±0.13 and 0.50±0.20 (mg/min/(mg/L)), Tpeak=12. 80±4.33 and 212.74±8.53 (min), Cmax=2.14±0.90 and 2. 03±0. 87 ( mg/L ) respectively. There was a significant difference for elimination half-time t1/2 β between the two groups (p<0.05) and there were no significant differences for the other pharmacokinetics parameters . The extent of spread varied among the patients with the median upper block level not exceeding T5 .The onset time and the duration of the sensory block in the patients with renal function failure were as followed : 10±2 (min) and 5.5 ±0. 5 (h), and the motor block were 20. 4±5 (min) and 3. 3 ±1 (h) . The onset time and the duration of the sensory block in thevolunteers with normal renal function were as followed : 11±1.5 (min) and 5.1±0.7 (h), and the motor block were 17±8 (min) and 3. 2±1. 2 (h) . The onset time and the duration of the sensory block in the patients of renal function failure were as followed 11±1. 5 (min) and 5.1±0.7 (h), and the motor block were 17±8 (min) and 3.2±1.2 (h) .The motor block had slower onset and shorter duration than sensory block in both groups. There were no significant differences between these two groups.Conclusions: The elimination half-time was longer in the patients with renal function failure than in the volunteers with normal renal function. This difference may be caused by a slower elimination of ropivacaine through kidney in patients with renal function failure . Our results suggest that ropivacaine dose shall be reduced accordingly in clinical practice for the patients with renal function failure.