Clinical, Pharmacokinetic, and Pharmacogenetic Determinants of Clopidogrel Resistance in Korean Patients with Acute Coronary Syndrome / 대한진단검사의학회지

BACKGROUND: Clopidogrel has been widely used to prevent recurrent ischemia in patients with acute coronary syndrome (ACS). However, inter-individual variability in response to clopidogrel has been a problem in the clinical setting. The aim of the present study was to investigate the frequency of clopidogrel resistance and to determine the clinical, pharmacokinetic, and pharmacogenetic factors for clopidogrel resistance in Korean patients with ACS. METHODS: Clinical information, such as the underlying diseases and concurrent medications, of 114 patients with ACS who received clopidogrel therapy was studied. The degree of inhibition of platelets was assessed using the VerifyNow assay (Accumetrics, USA). The patients who showed less than 20% inhibition of platelets were defined as non-responders to clopidogrel treatment. Steady state plasma concentrations of clopidogrel were measured using HPLC/tandem mass spectrometry. CYP2C19 genotyping was also performed. RESULTS: A wide inter-individual variability was observed in platelet inhibition (0-76%); 56 patients (49%) showed less than 20% inhibition. There were no differences between the patients' history of diabetes mellitus and concurrent medications as well as the plasma concentrations of clopidogrel of the responders and non-responders. CYP2C19 variants, including CYP2C19*2 and CYP2C19*3, were more commonly observed in the non-responders than in the responders (P value<0.0001). CONCLUSIONS: The response to clopidogrel was highly variable in Korean patients with ACS. The results of the present study confirmed that the genetic polymorphism of CYP2C19 could be important in clopidogrel response. However, further studies are required to investigate other likely factors involved in clopidogrel resistance.

A Case of Tertian Malaria which Recurred Three Times Despite Standard Chloroquine-primaquine Therapy / 감염

Plasmodium vivax malaria, which used to be endemic in the past, re-emerged in 1993 and the number of cases has increased annually. Though there has been no proven endemic drug-resistant malaria case reported, widespread use of anti-malarial chemoprophylaxis for the military personnel could cause emergence of resistance. We herein report a case of tertian malaria, which recurred three times despite the standard chloroquine-primaquine therapy. The patient is 40-year-old male, lives in Dongducheon city, Gyeonggy province, and has never been abroad. He visited hospital in September 2000, because of fever. His blood smear revealed ring forms and trophozoites of P. vivax. He took hydroxychloroquine for 3 days and primaquine for 14 days. His symptoms disappeared then. After 7 months he got fever for 2 days and his blood smear revealed schizonts of P. vivax. He took the same medicines and got well next day. Fever recurred 4 month later, and trophozoites were observed on the blood smear. Hydroxychloroquine and primaquine were prescribed in the same way and fever disappeared. Forty three days later, he had fever and positive blood smear of P. vivax trophozoite. Fever disappeared on the day drug was administered and no malaria was detected in follow up smear of 7 and 14 days. He was free of fever in follow up at 3 months later.