The pharmacokinetics of ropivacaine after intraperitoneal administration

Instillation versus nebulization

Delphine Betton, Nicolas Greib, Herve Schlotterbeck, Girish P. Joshi, Genevieve Ubeaud-Sequier, Pierre Diemunsch

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

BACKGROUND: Intraperitoneal local anesthetic administration provides perioperative analgesia during laparoscopic procedures. We compared the pharmacokinetics of intraperitoneal ropivacaine administered by instillation or nebulization. METHODS: A crossover study was performed on 5 pigs under standardized general anesthesia with a carbon dioxide pneumoperitoneum of 12 mm Hg for 1 hour. Each animal, acting as its own control, was studied twice with an 8-day interval and received, in a randomized sequence, 3 mg/kg ropivacaine either by intraperitoneal instillation at the time of pneumoperitoneum exsufflation or by continuous nebulization in the carbon dioxide insufflation tubing. Arterial blood samples were taken every 10 minutes up to 120 minutes, and then hourly up to 6 hours. Ropivacaine concentrations were measured using high-performance liquid chromatography with ultraviolet-visible detection. The plasma-free fraction was evaluated after plasma ultracentrifugation. Pharmacokinetic parameters were calculated using both noncompartmental and compartmental analysis. The mean values were compared using the Student t test, or Wilcoxon test for paired series. RESULTS: The data were described by a 1-compartment model for both ropivacaine administration techniques, with a delay of 10 minutes for the nebulization group. The maximal ropivacaine concentrations were 0.96 μ/4g/mL for the nebulization group and 0.92 μ/4g/mL for the instillation group (P ≤ 0.66). The ropivacaine absorption constant was lower in the nebulization group (0.043 vs 0.083 min, P ≤ 0.02). There were no differences in the elimination half-life, elimination constant, mean total body clearance, distribution volume, mean area under the curve, and mean residence time. The free fraction of ropivacaine was also similar in the 2 groups. CONCLUSIONS: The pharmacokinetic profile of ropivacaine nebulization is similar to direct intraperitoneal instillation, but with a lower absorption rate.

Original languageEnglish (US)
Pages (from-to)1140-1145
Number of pages6
JournalAnesthesia and Analgesia
Volume111
Issue number5
DOIs
StatePublished - Nov 2010

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Pharmacokinetics
Pneumoperitoneum
Carbon Dioxide
Insufflation
ropivacaine
Ultracentrifugation
Local Anesthetics
Analgesia
Cross-Over Studies
General Anesthesia
Area Under Curve
Half-Life
Swine
High Pressure Liquid Chromatography
Students

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

The pharmacokinetics of ropivacaine after intraperitoneal administration : Instillation versus nebulization. / Betton, Delphine; Greib, Nicolas; Schlotterbeck, Herve; Joshi, Girish P.; Ubeaud-Sequier, Genevieve; Diemunsch, Pierre.

In: Anesthesia and Analgesia, Vol. 111, No. 5, 11.2010, p. 1140-1145.

Research output: Contribution to journalArticle

Betton, Delphine ; Greib, Nicolas ; Schlotterbeck, Herve ; Joshi, Girish P. ; Ubeaud-Sequier, Genevieve ; Diemunsch, Pierre. / The pharmacokinetics of ropivacaine after intraperitoneal administration : Instillation versus nebulization. In: Anesthesia and Analgesia. 2010 ; Vol. 111, No. 5. pp. 1140-1145.
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abstract = "BACKGROUND: Intraperitoneal local anesthetic administration provides perioperative analgesia during laparoscopic procedures. We compared the pharmacokinetics of intraperitoneal ropivacaine administered by instillation or nebulization. METHODS: A crossover study was performed on 5 pigs under standardized general anesthesia with a carbon dioxide pneumoperitoneum of 12 mm Hg for 1 hour. Each animal, acting as its own control, was studied twice with an 8-day interval and received, in a randomized sequence, 3 mg/kg ropivacaine either by intraperitoneal instillation at the time of pneumoperitoneum exsufflation or by continuous nebulization in the carbon dioxide insufflation tubing. Arterial blood samples were taken every 10 minutes up to 120 minutes, and then hourly up to 6 hours. Ropivacaine concentrations were measured using high-performance liquid chromatography with ultraviolet-visible detection. The plasma-free fraction was evaluated after plasma ultracentrifugation. Pharmacokinetic parameters were calculated using both noncompartmental and compartmental analysis. The mean values were compared using the Student t test, or Wilcoxon test for paired series. RESULTS: The data were described by a 1-compartment model for both ropivacaine administration techniques, with a delay of 10 minutes for the nebulization group. The maximal ropivacaine concentrations were 0.96 μ/4g/mL for the nebulization group and 0.92 μ/4g/mL for the instillation group (P ≤ 0.66). The ropivacaine absorption constant was lower in the nebulization group (0.043 vs 0.083 min, P ≤ 0.02). There were no differences in the elimination half-life, elimination constant, mean total body clearance, distribution volume, mean area under the curve, and mean residence time. The free fraction of ropivacaine was also similar in the 2 groups. CONCLUSIONS: The pharmacokinetic profile of ropivacaine nebulization is similar to direct intraperitoneal instillation, but with a lower absorption rate.",
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AB - BACKGROUND: Intraperitoneal local anesthetic administration provides perioperative analgesia during laparoscopic procedures. We compared the pharmacokinetics of intraperitoneal ropivacaine administered by instillation or nebulization. METHODS: A crossover study was performed on 5 pigs under standardized general anesthesia with a carbon dioxide pneumoperitoneum of 12 mm Hg for 1 hour. Each animal, acting as its own control, was studied twice with an 8-day interval and received, in a randomized sequence, 3 mg/kg ropivacaine either by intraperitoneal instillation at the time of pneumoperitoneum exsufflation or by continuous nebulization in the carbon dioxide insufflation tubing. Arterial blood samples were taken every 10 minutes up to 120 minutes, and then hourly up to 6 hours. Ropivacaine concentrations were measured using high-performance liquid chromatography with ultraviolet-visible detection. The plasma-free fraction was evaluated after plasma ultracentrifugation. Pharmacokinetic parameters were calculated using both noncompartmental and compartmental analysis. The mean values were compared using the Student t test, or Wilcoxon test for paired series. RESULTS: The data were described by a 1-compartment model for both ropivacaine administration techniques, with a delay of 10 minutes for the nebulization group. The maximal ropivacaine concentrations were 0.96 μ/4g/mL for the nebulization group and 0.92 μ/4g/mL for the instillation group (P ≤ 0.66). The ropivacaine absorption constant was lower in the nebulization group (0.043 vs 0.083 min, P ≤ 0.02). There were no differences in the elimination half-life, elimination constant, mean total body clearance, distribution volume, mean area under the curve, and mean residence time. The free fraction of ropivacaine was also similar in the 2 groups. CONCLUSIONS: The pharmacokinetic profile of ropivacaine nebulization is similar to direct intraperitoneal instillation, but with a lower absorption rate.

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