Nirmatrelvir
Nirmatrelvir. SARS-CoV-2 main protease (3CLpro / Mpro) inhibitor — blocks polyprotein cleavage. Co-administered with low-dose ritonavir as… Oral half-life 6.8 h.
SARS-CoV-2 main protease (3CLpro / Mpro) inhibitor — blocks polyprotein cleavage. Co-administered with low-dose ritonavir as Paxlovid to inhibit nirmatrelvir's CYP3A4 metabolism. Major DDI engine via the ritonavir component during the 5-day course.
PK: CLASS 6 IN ITS UNAMBIGUOUS FORM. The Paxlovid label reports, for nirmatrelvir given with ritonavir, "V z /F (L), mean 104.7" with its own abbreviation key spelling out that Vz/F is the APPARENT volume of distribution — and the record stored that figure beside an F of 0.5, dividing by an availability twice. There is no human intravenous nirmatrelvir, absolute bioavailability has never been determined, and 0.5 has no source; this is not one of the reversible class-6 judgements. The damage is measured against the record OWN cited abstract: "Geometric mean nirmatrelvir Cmax and AUC were 3.08 microg/mL and 19.66 microg.h/mL after the first dose and increased to 4.50 microg/mL and 32.01 microg.h/mL at steady state ... a mean terminal half-life of 6.84 h" — against which the stored record was 2.2x low on exposure and 2.9x low on peak. The half-life also becomes that verbatim 6.84. I CONSIDERED AND REJECTED THE elvitegravir PRECEDENT: that record was stripped because its boosted and unboosted states differ threefold with no way to declare which, whereas nirmatrelvir has NO CLINICAL UNBOOSTED STATE and every label figure is already measured with ritonavir. There is nothing ambiguous to declare.
Pharmacokinetics
- Oral — t½ 6.8 h · F 100% · ka 1.422 h⁻¹ · Vd 104.7 L
Sources: PMID:42090083