Lipid Solubility of Pancuronium and Vecuronium Determined by N-Octanol/Water Partitioning

Weindlmayr-Goettel, M.; Gilly, H.; Sipos, Emese; Steinbereithner, K

doi:10.1093/bja/70.5.579

Cited by 7 publications

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“…Vecuronium has weak to moderate lipophilic property due to its steroidal structure and is mainly distributed in lean tissues. [ 1 14 ] Obese patients have larger lean body mass and fat mass than lean patients. [ 3 ] Therefore, when vecuronium is given based on RBW, it results in over dosing and prolonged duration of action.…”

Section: Discussionmentioning

confidence: 99%

Comparison of neostigmine induced reversal of vecuronium in normal weight, overweight and obese female patients

2015

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Background and Aims:Obese patients are more vulnerable to residual neuromuscular block (NMB) and its associated complications in the post-operative period. This study was carried out to compare neostigmine induced reversal of vecuronium in normal weight, overweight and obese female patients, objectively using neuromuscular (NM) monitoring.Methods:Twenty female patients each belonging to normal weight, overweight and obese, based on body mass index, requiring general anaesthesia were recruited for this prospective cross sectional study. NMB was induced with vecuronium (0.1 mg/kg) dose based on patient's real body weight (RBW) and monitored using acceleromyographic train of four (TOF). All patients received neostigmine 40 μg/kg and glycopyrrolate 10 μg/kg at 25% of spontaneous recovery of first twitch height (T1) of TOF (DUR 25%) and were allowed to recover to TOF ratio of 0.9. Statistical analysis was done using analysis of variance test.Results:Recovery of TOF ratio to 0.5 was comparable in all three groups. Recovery of TOF ratio to 0.7 was delayed in obese (9.82 ± 3.21 min) compared with normal weight group (7.50 ± 2.52 min). Recovery of TOF to 0.9 was significantly delayed in both overweight (12.18 ± 4.29 min) and obese patients (13.78 ± 4.30 min). DUR 25% was significantly longer in overweight (mean, standard deviation [range]; 30.10 [19–40 min]) and obese (28.8 [12–45 min]) compared with normal weight patients (22.75 [16–30 min]).Conclusion:In overweight and obese patients, when vecuronium induction dose is based on RBW, neostigmine induced recovery of NMB is delayed in late phases (TOF 0.7-0.9), which may result in vulnerability for associated complications of incomplete recovery. Ensuring safe recovery thus requires objective NM monitoring.

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Section: Discussionmentioning

confidence: 99%

Comparison of neostigmine induced reversal of vecuronium in normal weight, overweight and obese female patients

2015

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Effect of Electrolytes on Octanol‐Water Partition Coefficients: Calculations with COSMO‐RS

et al. 2010

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In this work, the possibility of the a priori predictive model COSMO-RS to describe partitioning of pharmaceutically active compounds in the octanol-water system (P OW ) in the presence of electrolytes is investigated. It is shown that the calculated values of P OW depend on the pH and the ionic strength of the solution for both dissociated and non-dissociated solutes. Whereas the partitioning of the non-dissociated form in the presence of salts or buffers can be explicitly described by COSMO-RS, the partitioning of the ionized pharmaceuticals is taken into account by their dissociation constants. Overall, reasonable agreement with experimental values is achieved. Principally, these types of calculations can be extended to other two-phase systems used for extraction and formulations of pharmaceuticals and further organic solutes. IntroductionPartition coefficients of organic solutes in the octanol-water system play an important role in chemical engineering and the pharmaceutical industry, being one of the standards to characterize the lipophilicity of a given substance. Therefore, methods to predict partition coefficients are of special value, especially those which are based on structural information and require no further experimental data. Among those, the method of Leo and Hansch (ClogP) became widespread in the scientific community because of its simplicity and high availability of the model parameters [1]. Besides this, thermodynamics-based models for the prediction of activity coefficients, like UNIFAC (UNIFAC-Kow) [2] and COSMO-RS [3], were successfully used for this purpose. A large number of octanolwater and other solvent-water partition coefficients of different solute classes were well predicted with COSMO-RS [4,5]. However, the presence of ions in the form of salts, buffers, or dissociated solutes limits the modeling possibilities considerably. The Leo and Hansch model is not able to describe the influence of electrolytes on the solute partitioning explicitly, whereas UNIFAC (modification for electrolytes) [6 and citations therein] and COSMO-RS [3], as well as several QSAR models [7] are principally able to do so. The ability of COSMO-RS to describe systems containing ionic compounds was demonstrated for the systems containing ionic liquids and ionic surfactants [5,8]. Although the prediction of the activity coefficients of single ions is not directly possible, activity coefficients of neutral compounds in the presence of ions can be calculated.The purpose of this work is to prove the applicability of COSMO-RS to the prediction of the change of partition coefficients of both neutral and dissociating organic substances as a function of pH and salt concentration in the solution. Since the pH influence on partitioning is especially important in the area of drug development, the calculations are performed for pharmaceutically active compounds. Methods COSMO-RSThe COSMO-RS model (Conductor-like Screening Model for Real Solvents) allows for an a priori prediction of thermodynamic properties, such as activ...

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Management of Neuromuscular Blockade in the Elderly and Morbidly Obese Patient: What Does the Data Show?

Renew

Naguib

2020

Curr Anesthesiol Rep

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Lipid Solubility of Pancuronium and Vecuronium Determined by N-Octanol/Water Partitioning

Cited by 7 publications

References 0 publications

Comparison of neostigmine induced reversal of vecuronium in normal weight, overweight and obese female patients

Comparison of neostigmine induced reversal of vecuronium in normal weight, overweight and obese female patients

Effect of Electrolytes on Octanol‐Water Partition Coefficients: Calculations with COSMO‐RS

Management of Neuromuscular Blockade in the Elderly and Morbidly Obese Patient: What Does the Data Show?

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