Hydroxychloroquine
Hydroxychloroquine. Aminoquinoline antimalarial — accumulates in lysosomes raising endosomal pH. Disrupts antigen processing + Toll-like receptor… Oral half-life 40 d.
Aminoquinoline antimalarial — accumulates in lysosomes raising endosomal pH. Disrupts antigen processing + Toll-like receptor signaling. Used long-term for SLE + rheumatoid arthritis. Retinopathy risk requires baseline + annual ophthalmologic monitoring.
PK: A MATRIX ARTEFACT WORTH 9.06x, AND MY OWN PRIOR WOULD HAVE PRESERVED IT. Hydroxychloroquine is reported in either whole blood or plasma and the two differ about sevenfold — "Blood to plasma concentration ratios were not constant (mean +/- s.d.: 7.2 +/- 4.2)" — and the source states both volumes side by side: "large volumes of distribution were calculated (5,522 l FROM BLOOD, 44,257 l FROM PLASMA)". The stored 50,000 was NEITHER: a rounded plasma-scale volume welded to a blood-derived bioavailability, since F 0.74 is verbatim "estimated from the blood and urine data" and that same abstract disqualifies the plasma route to it. Each matrix is internally consistent to within eight percent against its own clearance, 96 mL/min in blood and 667 in plasma; MIXING THEM WAS THE ENTIRE DEFECT. THE FIGURE I SUPPLIED IN THE PROMPT, 40,000-50,000 L, IS THE PLASMA NUMBER — real, but unusable beside a blood-derived F, so adopting it would have preserved the error. CLASS 6 IS ACQUITTED because an intravenous infusion was actually given. A CAVEAT IS RECORDED: this blood volume is a terminal one and under-predicts the observed peak; a whole-blood population model exists that reproduces the peak but at a half-life discarding the forty-day terminal phase, and one compartment cannot hold both. DOSING: A SALT-FACTOR MISMATCH STACKED ON TOP OF THE MATRIX ERROR. mw_g_mol 335.87 is the FREE BASE, but the stored 200/400/600 mg were SULPHATE doses, so the record fed a salt dose into a base-referenced model — a further 1.29x overstatement. Its own source states the conversion verbatim: "a 155 mg oral tablet and an intravenous infusion of 155 mg racemic hydroxychloroquine (200 mg hydroxychloroquine sulphate)". The dose block is converted to base at that stated ratio rather than the mass being changed, because every PK value on this record describes the base.
Pharmacokinetics
- Oral — t½ 40.0 d · F 74% · ka 2.466 h⁻¹ · Vd 5522 L
Sources: PMID:2757893, PMID:3179169