I want to have the volume of distribution of vancomycin but I found variable amounts between 0.5, 0.7, and 0.9 L/Kg in different references. What is the best value in critically ill patients? And why it is depend on actual body weight not lean body mass?
Dear Parisa Ghasemiyeh,
If you check paper below variability of vancomycin Vd depending on what kind of Vd is calculated could be different and shown high variability. In this specific study RSD% for Vc is 52.28.Variable tissue distribution is important factor that affect its clinical activity (see second reference).
" Vancomycin is a relatively hydrophilic antibiotic. In critically ill patients, the leakage of the fluid from the vessels may result in the larger volume of vancomycin distribution, as well as decrease its plasma drug concentration"
Article The pharmacokinetics of vancomycin during the initial loadin...
https://academic.oup.com/cid/article/42/Supplement_1/S35/275535
Vancomycin is hydrophilic compound with XlogP -2.6 consequently fat should have minimal impact on vancomycin volume of distribution.
https://pubchem.ncbi.nlm.nih.gov/compound/14969#section=Chemical-and-Physical-Properties
Hope it helps,
Best regards
Tomasz
nice question but complicated. In essence, this depends on the characteristics of the drug compound and on the characteristics of the patient. For vancomycin, there is protein binding in plasma (albumin and IgA dependent), and the subsequent distribution will also depend on the body composition (difference in water content). Both factors explain eg differences between neonates to children or adults, and critically ill patients to non-critically ill cases. Some potential useful references (some are open access, otherwise ask me for the papers)
Pharmacokinetic modelling and Bayesian estimation-assisted decision tools to optimize vancomycin dosage in neonates: only one piece of the puzzle.
Allegaert K, Flint R, Smits A.
Expert Opin Drug Metab Toxicol. 2019 Aug 19:1-15. doi: 10.1080/17425255.2019.1655540
Vancomycin Pharmacokinetics Throughout Life: Results from a Pooled Population Analysis and Evaluation of Current Dosing Recommendations.
Colin PJ, Allegaert K, Thomson AH, Touw DJ, Dolton M, de Hoog M, Roberts JA, Adane ED, Yamamoto M, Santos-Buelga D, Martín-Suarez A, Simon N, Taccone FS, Lo YL, Barcia E, Struys MMRF, Eleveld DJ.
Clin Pharmacokinet. 2019 Jun;58(6):767-780. doi: 10.1007/s40262-018-0727-5
Factors impacting unbound vancomycin concentrations in different patient populations.
Oyaert M, Spriet I, Allegaert K, Smits A, Vanstraelen K, Peersman N, Wauters J, Verhaegen J, Vermeersch P, Pauwels S.
Antimicrob Agents Chemother. 2015 Nov;59(11):7073-9. doi: 10.1128/AAC.01185-1
Factors impacting unbound vancomycin concentrations in neonates and young infants.
Smits A, Pauwels S, Oyaert M, Peersman N, Spriet I, Saegeman V, Allegaert K.
Eur J Clin Microbiol Infect Dis. 2018 Aug;37(8):1503-1510.
Dear Prof. Karel Allegaert and Prof. Tomasz Grabowski
Thanks for your useful comments.
Best regards
Parisa
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