Elevated PT, APPT and PT/INR possibly associated with doxycycline and cefoperazone co-administration: A case report.

WHAT IS KNOWN AND OBJECTIVE: Little is known regarding changes in blood coagulation parameters associated with tetracycline antibiotics. We report a possible case of elevated PT, APPT and PT/INR associated with doxycycline and cefoperazone co-administration. CASE SUMMARY: An 83-year-old Chinese male inpatient with severe pneumonia, chronic renal insufficiency and malnutrition experienced elevated PT, APPT and PT/INR which occurred within a few days of doxycycline added to his cefoperazone treatment and returned to normal after removal of it. WHAT IS NEW AND CONCLUSION: Very close monitoring of coagulation parameters might be advisable in those subjects when administering doxycycline and cefoperazone concomitantly.

The Elimination Rate after Clozapine Overdose in Chinese Schizophrenia Patients: A Population Pharmacokinetics Model Study.

INTRODUCTION: The prescribing of clozapine in China is common because of its outstanding efficacy and low price. There have been many cases of clozapine overdose in China. However, studies about the pharmacokinetics after overdose in the Chinese have rarely been reported. Population pharmacokinetics (PopPK) can analyze sparse data, and it is appropriate to compute clozapine pharmacokinetics after overdose. METHODS: There were 47 clozapine overdose cases. We constructed a single-compartment first-order elimination PopPK model. We also considered some covariates that can influence the pharmacokinetics parameters. RESULTS: 21 cases were included in the analysis. When the reported toxic dosage was 3,740 mg, the elimination rate constant of the population was 0.0258(h(-1)). The elimination half-life was 26.9 h. The coefficient of random variation was 17%. DISCUSSION: PopPK can solve the problem of sparse data after overdose. The area under the concentration-time curve after clozapine overdose exhibited the "two peaks phenomenon." The reported toxic dosage could impact clozapine elimination after overdose. Delayed absorption of clozapine is the best explanation for this finding.

Relative bioequivalence evaluation of two oral atomoxetine hydrochloride capsules: a single dose, randomized, open-label, 2-period crossover study in healthy Chinese volunteers under fasting conditions.

To evaluate the bioequivalence of a new formulation of atomoxetine hydrochloride (CAS 82248-59-7) capsules (test) and an available branded capsules (reference) after administration of a single 40 mg dose, randomized, open-label, 2-period crossover study was conducted in 22 healthy male Chinese subjects with a 1-week wash-out period. This study was designed for/the Honglin Pharmaceutical Co. Ltd and contracted to be done by the Beijing Anding Hospital in order to satisfy Chinese regulatory requirements to allow marketing of this generic product and performed according to the criteria of SFDA. Blood samples were collected before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16 and 24 h after drug administration. Plasma concentrations were determined by high-performance liquid chromatography (HPLC) with UV detection. A non-compartmental method was used to calculate the pharmacokinetic parameters and evaluate bioequivalence of the 2 formulations. The 90% confidence interval (CI) of the ratios (test/reference) of atomoxetine for AUC0-24, AUC0-∞ and Cmax were 100.9% (93.6-108.8%), 103.1% (95.1-111.7%) and 105.2% (92.8-119.4%), respectively, which fell within the interval of 80-125% and 75-133%. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. From these results it can be concluded that the test formulation of atomoxetine capsules met the regulatory criterion for bioequivalence to the reference formulation.