Excretion

Chloroquine is eliminated very slowly. The pharmacokinetics of chloroquine excretion can be described with a multicompartmental model. The plasma concentrations fall poly-exponentially, that is, fast in the beginning and then slowly in the terminal phase. This elimination is prolonged with higher dosages. Therefore, the reported half-lives differ between 74.7 and 30.1 h, 146 to 325 h, and 32 days depending on dosage and the reference to the poly-exponential decrease (e. g., early or late terminal half-life time).

Forty percent to 70% of chloroquine is excreted unchanged with urine. The percentage is higher in acidic than in alkaline urine. The mean value of the total clearance of chloroquine reaches 0.35 l/kg per hour. An impaired kidney function prolongs the half-life time significantly. Chloroquine itself and, to a lesser extent, hydroxychloroquine, can impair creatinine clearance by 10%, which can reduce chloroquine excretion, especially in older patients. In these instances, an increased rate of side effects has to be expected owing to the accumulation of chloroquine, and the dosage has to be reduced.

Twenty-five percent to 40% of chloroquine is metabolized in the liver via cytochrome P450 enzymes to the pharmacologically active metabolites desethyl chloroquine and bisdesethyl chloroquine. Their plasma concentrations reach ca. 33%-40% and 10% of the chloroquine concentrations, respectively. Findings from animal experiments hinted at a stereoselectivity with respect to the binding to proteins (S[+]chloroquine 67%, R[-]chloroquine 35%) as well as to the clearance (faster metabolism and excretion of S[+]enantiomers). Corresponding differences in the clinical effects in men, however, were not reported up to now.

Five percent to 10% of chloroquine is excreted unchanged with the feces. The elimination of chloroquine is limited by the back diffusion of the substance from deep compartments into plasma. After a single dose, small amounts of chloroquine can be found in plasma and erythrocytes even after 56 days. After prolonged therapy, chloroquine could be detected in the plasma, erythrocytes, and urine of patients even 5 years after the last intake.

Quinacrine is slowly eliminated from the body. Less than 11% is eliminated in the urine daily. Significant amounts of quinacrine can still be detected in the urine for at least 2 months after therapy is discontinued.

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