Journal of Pharmacology and Pharmacotherapeutics

RESEARCH PAPER
Year
: 2019  |  Volume : 10  |  Issue : 1  |  Page : 22--32

Pharmacokinetic modeling of propofol in Indian children


B Naveen Naik1, Preethy J Mathew2, Smita Pattanaik3, Venkateswari Muthukrishnan4, Goverdhan Dutt Puri2 
1 Department of Anaesthesiology and Critical Care, JIPMER, Puducherry, India
2 Department of Anaesthesia and Intensive Care, PGIMER, Chandigarh, India
3 Department of Pharmacology, PGIMER, Chandigarh, India
4 Certara USA, Inc., Princeton, NJ, USA

Correspondence Address:
Goverdhan Dutt Puri
Department of Anaesthesia and Intensive Care, PGIMER, Chandigarh
India

Objective: To analyse the PK (pharmacokinetics) of propofol after single bolus dose in children undergoing elective general surgery and to establish a PK model of propofol after single bolus dose in children undergoing elective general surgery and to establish a PK model of propofol. Materials and Methods: Twelve healthy Indian children aged 5–12 years who underwent elective general surgery under general anesthesia received propofol at an intravenous bolus dose of 2.5 mg/kg. The plasma propofol concentration over the next 12 h was estimated using high-performance liquid chromatography. A total of 144 samples were analyzed, and PK parameters were evaluated using nonlinear mixed-effects modeling. Results were validated using bootstrap analysis, and visual predictive check was done to evaluate the final model. Results: Propofol PK in Indian children was characterized by a three-compartment model similar to adults. The model derived estimates of PK parameters are as follows: volume of the central compartment (V1) = 598.73 ml/kg, volume of the second compartment (V2) = 821.12 ml/kg, volume of the third compartment (V3) = 1097 ml/kg, systemic clearance (CL1) = 22.1 ml/kg/min, and intercompartmental clearances CL2 and CL3 which were 42.5 ml/kg/min and 10.4 ml/kg/min, respectively. Conclusion: The final PK model imparted a robust characterization of propofol PK. Inclusion of body weight as a covariate to the model exhibited a significant impact on propofol PK. The execution of this patient derived PK model should support future population PK studies that include diverse population with sparse sampling to support the dosing of propofol in Indian children undergoing surgery under total intravenous anesthesia.


How to cite this article:
Naik B N, Mathew PJ, Pattanaik S, Muthukrishnan V, Puri GD. Pharmacokinetic modeling of propofol in Indian children.J Pharmacol Pharmacother 2019;10:22-32


How to cite this URL:
Naik B N, Mathew PJ, Pattanaik S, Muthukrishnan V, Puri GD. Pharmacokinetic modeling of propofol in Indian children. J Pharmacol Pharmacother [serial online] 2019 [cited 2020 Oct 30 ];10:22-32
Available from: http://www.jpharmacol.com/article.asp?issn=0976-500X;year=2019;volume=10;issue=1;spage=22;epage=32;aulast=Naik;type=0