RESUMO
A lumbar puncture can be used to measure the concentrations of drugs and/or pharmacodynamic biomarkers during clinical trials of central nervous system drugs. We report a case of a post lumbar puncture headache (PLPH) in a first-in-human study, which was reported as a serious adverse event. A 20-year-old man received 200 mg of the investigational product (IP) for 7 days and underwent a lumbar puncture for cerebrospinal fluid sampling before IP administration (Day 1, pre-dose) and after 7 days and multiple IP administrations (Day 7, 1 hour post-dose). After discharge on Day 8, the subject complained of headache, nausea, vomiting, neck stiffness, and numbness of the extremities. The symptoms occurred when he got up and disappeared after he remained in the supine position for several minutes. Five days later, he visited the neurology clinic of the main hospital. The neurologist recommended hospitalization for further evaluation and symptom management, and the subject was then admitted to the hospital. There were no abnormal findings in vital signs, laboratory results, or brain-computed tomography. His symptoms disappeared during the hospitalization period. It was important to distinguish whether the headache was IP-related or lumbar puncture-related. Therefore, knowledge of clinical characteristics and differential diagnosis of PLPH is paramount. Furthermore, if severe PLPH occurs, a consultation with a neurologist and imaging studies should be considered for a differential diagnosis of PLPH.
RESUMO
Brown adipose tissue (BAT) is related with energy expenditure, in contrary to fat-storing white adipose tissue. Recent studies have shown that cold exposure could be related with the expression of BAT in adult subjects assessed by ¹8F-fluorodeoxyglucose (FDG) positron emission tomography (PET). In addition, the application in previous clinical trials showed positive effect of xanthigen containing fucoxanthin and punicic acid on body weight and liver fat content. In this short-term intervention study, we evaluated the effect of xanthigen on the expression of BAT by ¹8F-FDG PET. Two healthy obese premenopausal women were enrolled and xanthigen 600 mg (2 capsules including fucoxanthin 3 mg, punicic acid 174 mg) was given for 3 months without dietary and exercise intervention. Body composition and dietary intake were assessed monthly. Laboratory test and ¹8F-FDG PET were performed before and after intervention. After intervention, there was neither weight reduction nor remarkable laboratory change. However, BAT, assessed by ¹8F-FDG PET, was detected in both cervical, supraclavicular and paravertebral space in one subject, even though her body weight showed mild increase. This result suggested that xanthigen can induce BAT in a healthy adult. However, a further large well-controlled study is needed.
RESUMO
It is well known that the CYP2C19 genetic polymorphism influences the pharmacokinetics and pharmacodynamics of proton pump inhibitors (PPIs), but no report has addressed the effects on ilaprazole, a newly developed PPI. To investigate the effects of the CYP2C19 genetic polymorphism on the disposition and pharmacodynamics of ilaprazole, multiple doses of once-daily 10 mg ilaprazole were repeatedly administered for 7 days to 27 healthy Korean participants, comprising 9 homozygous CYP2C19 extensive metabolizers (homo EMs), 10 heterozygous EMs (hetero EMs), and 8 homozygous poor metabolizers (PMs). The plasma concentration and pharmacodynamic response were measured in the last dose interval. Each genotype group was matched for gender and thus was composed of 4 male and 4 female participants when the analysis was conducted. The pharmacokinetic parameters estimated from the plasma concentrations of ilaprazole and its metabolite ilaprazole sulfone, the serum gastrin level, and the 24-hour intragastric pH were compared among the CYP2C19 genotype groups. No statistically significant differences in the maximum plasma concentration at steady state(C(ss,max)) and the area under the concentration-time curve from zero to 24 hours (AUC(τ)) of ilaprazole and ilaprazole sulfone were observed among the homo EM, hetero EM, and PM CYP2C19 genotypes. In addition, the mean 24-hour intragastric pH, the percentage of time at pH >4, and the AUC(τ) of serum gastrin showed no significant differences among the CYP2C19 genotype groups. The data suggests that the pharmacokinetics and pharmacodynamics of ilaprazole are not significantly influenced by the CYP2C19 genetic polymorphism in healthy participants.
