V03: All other therapeutic products

ATC V03 all other therapeutic products for modelers: typical structure, reversal agents; reversal can wear off first.
Modified

September 22, 2026

Typical structure, reversal agents. Sugammadex encapsulates rocuronium and the complex is cleared by the kidney, so clearance of both falls in renal impairment [1]. A population analysis nonetheless found renal function did not affect reversal time [2]. The fitted model is complex formation using the in vitro dissociation constant, with effect driven by the fall in free rocuronium rather than by an Emax on sugammadex [3].

Reversal can wear off first. The short duration of action of naloxone is a pharmacokinetic property, so reversal can wear off while the opioid is still present [4]. Judging a reversal dose therefore calls for a mechanistic model linking both drugs to ventilation [5].

References

[1]
Staals LM, Snoeck MMJ, Driessen JJ, Hamersvelt HW van, Flockton EA, Heuvel MW van den, et al. Reduced clearance of rocuronium and sugammadex in patients with severe to end-stage renal failure: A pharmacokinetic study. British Journal of Anaesthesia 2010;104:31–9. https://doi.org/10.1093/bja/aep340.
[2]
Kleijn HJ, Zollinger DP, Heuvel MW van den, Kerbusch T. Population pharmacokinetic-pharmacodynamic analysis for sugammadex-mediated reversal of rocuronium-induced neuromuscular blockade. British Journal of Clinical Pharmacology 2011;72:415–33. https://doi.org/10.1111/j.1365-2125.2011.04000.x.
[3]
Ploeger BA, Smeets J, Strougo A, Drenth H-J, Ruigt G, Houwing N, et al. Pharmacokinetic-pharmacodynamic model for the reversal of neuromuscular blockade by sugammadex. Anesthesiology 2009;110:95–105. https://doi.org/10.1097/ALN.0b013e318190bc32.
[4]
Ngai SH, Berkowitz BA, Yang JC, Hempstead J, Spector S. Pharmacokinetics of naloxone in rats and in man: Basis for its potency and short duration of action. Anesthesiology 1976;44:398–401. https://doi.org/10.1097/00000542-197605000-00008.
[5]
Yang TE, Del Bene F, Lavezzi SM, Iavarone L, Zhang J, Kim J, et al. Mechanistic pharmacokinetic-pharmacodynamic modeling and simulations of naloxone auto-injector 10 mg reversal of opioid-induced respiratory depression. CPT: Pharmacometrics & Systems Pharmacology 2024;13:1722–33. https://doi.org/10.1002/psp4.13215.