A Chinese medicine called Danggui Longhui may be a new clinically relevant clozapine inducer: Two case reports identified by therapeutic drug monitoring

Background: Danggui Longhui is a traditional Chinese medicine made from the dried root of Angelica sinensis. It is used in psychiatric patients in China to reduce associated constipation. In a population pharmacokinetic model in olanzapine patients from Beijing Anding Hospital, we demonstrate that dangguilonghui tablets doubled olanzapine clearance, indicating the induction of olanzapine metabolism. Olanzapine metabolism is similar to clozapine metabolism. Methods: Two cases of possible clozapine induction using dangguilonghui tablets 4 g/day were identified in Beijing Anding Hospital. Dividing the minimum therapeutic concentration of 350 ng/mL by the concentration-to-dose (C/D) ratio provides the minimum therapeutic dose. Results: Case 1 was a female smoker on clozapine for 415 days. The mean of 6 clozapine C/D ratios associated with smoking provided a minimum therapeutic dose of 267 mg/day. There were 6 steady-state concentrations on the combination of valproic acid and dangguilonghui tablets, which provided a much higher minimum therapeutic dose of 833 mg/day. Four steady-state clozapine C/D ratios based on smoking and valproate after 4 months of carbamazepine 200 mg/day provided a minimum therapeutic dose of 603 mg/day. Case 2 was a female non-smoker on clozapine for 58 days. She had 3 clozapine C/D ratios on dangguilonghui tablets with a mean of 0.30 ng/mL providing a minimum therapeutic dose of 1167 mg/day. Conclusion: Future clinical studies with repeated measures need to replicate the possibility that dangguilonghui tablets are a moderate-to-strong inducer of clozapine metabolism as suggested by these two limited cases.