Overview/Clinical Pharmacology

Thiola^® is an active reducing agent which undergoes thiol-disulfide exchange with cystine to form a mixed disulfide of Thiola-cysteine.

2R-SH + R′-S-S-R′ 2R-S-S-R′ + 2H⁺

Thiola Cystine Thiola-cysteine

From this reaction, a water-soluble mixed disulfide is formed and the amount of sparingly soluble cystine is reduced. When Thiola^® is given orally, up to 48% of dose appears in urine during the first 4 hours and up to 78% by 72 hours. Thus, in patients with cystinuria, sufficient amount of Thiola^® or its active metabolites could appear in urine to react with cystine, lowering cystine excretion.

The decrement in urinary cystine produced by Thiola^® is generally proportional to the dose. A reduction in urinary cystine of 250-350 mg/day at a Thiola^® dosage of 1 g/day, and a decline of approximately 500 mg/day at a dosage of 2 g/day, might be expected. Thiola^® causes a sustained reduction in cystine excretion without apparent loss of effectiveness. Thiola^® has a rapid onset and offset of action, showing a fall in cystine excretion on the first day of administration and a rise on the first day of drug withdrawal.