Toxicokinetics

Hydroxychloroquine has a large volume of distribution (44,257L)³.

Drug distribution occurs in three phases: distribution from blood to tissues, equilibration between blood and tissues, and release from tissues back into blood⁴.

Hydroxychloroquine binds to both albumin and alpha-glycoprotein in the blood and so blood concentration peaks shortly after absorption but falls again relatively quickly due to rapid partitioning into organs⁵.

As a weak base, hydroxychloroquine accumulates in particular within acidic vesicles such as lysosomes⁵.

Hydroxychloroquine also binds strongly to melanin and can deposit in melanin-​containing tissues such as the skin and the eyes and hence may explain hydroxychloroquine retinopathy³.

Distribution patterns observed in animal studies show that all tissue to blood concentrations were ≥1, with the Kp _tissue/blood ratio for the various tissues observed in the descending order of liver, thymus, spleen, kidney, lung, heart, subcutaneous fat and brain⁶.

Hydroxychloroquine is excreted in a number of different ways. The majority of the drug is excreted by the kidneys and the liver, with between 40-60% of the drug lost through the kidneys (approximately 20% of which is unchanged) via the urine^4,7. 16-25% is excreted unchanged through the faeces, 5% is removed through skin shedding, and between 25-45% of the drug is stored in lean body tissues^4,7.

Since alkalinisation of the urine decreases excretion, ammonium chloride could be given orally in order to acidify the urine and increase renal excretion by 20-80%^4,7. Please note this approach is not used in clinical practice to treat chloroquine retinopathy⁴.