Chaveewan Ratanajamit

Adverse pregnancy outcome in women exposed to acyclovir during pregnancy: a population-based observational study.

This study aimed to examine the risk of adverse pregnancy outcomes in children born to mothers who redeemed a prescription for systemic or topical acyclovir during pregnancy. Data on prescriptions of acyclovir were obtained from the Danish North Jutland Prescription Database and data on pregnancy outcomes from the Danish Medical Birth Registry and the County Hospital Discharge Registry. The risk of malformations, low birth weight, preterm birth and stillbirth in users of acyclovir were compared with non-exposed women using a follow-up design, while the risk of spontaneous abortion was examined using a case-control design. 90 pregnant women had redeemed a prescription for systemic acyclovir, and 995 women for topical acyclovir, during 30 d before conception, or during their pregnancies from 1 January 1990 to 31 December 2001. The odds ratios (95% confidence intervals) of the exposed relative to the non-exposed for the systemic and topical acyclovir were: malformations, 0.69 (0.17-2.82) and 0.84 (0.51, 1.39); low birth weight, 2.03 (0.50-8.35) and 0.48 (0.21-1.07); preterm birth, 1.04 (0.38-2.85) and 0.95 (0.70-1.28); stillbirth (for topical acyclovir), 1.70 (0.80-3.60); and spontaneous abortion, 2.16 (0.60-7.80) and 1.29 (0.80-3.60). There is increasing evidence that the use of systemic acyclovir is not associated with an increased prevalence of malformations at birth and preterm delivery. The data for low birth weight and spontaneous abortion are still inconclusive, although the risk of spontaneous abortion is increased in women exposed to acyclovir during the first month of pregnancy. The use of topical acyclovir does not seem to be associated with any adverse pregnancy outcome, although data on stillbirth are inconclusive.

Metronidazole and risk of acute pancreatitis: a population-based case-control study.

Background : Use of metronidazole has been suggested to be associated with an increased risk of acute pancreatitis in case reports.

Valproic acid and risk of acute pancreatitis : A population-based case-control study

To examine whether acute pancreatitis is associated with use of valproic acid. Through the population-based hospital discharge registries we identified all patients with an incident hospitalization of acute pancreatitis in the counties of North Jutland (data 1991 to 2003), Aarhus (data 1996 to 2003), and Viborg (data 1998 to 2003), Denmark. From the Danish Civil Registration System, we selected 10 sex-matched and age-matched population controls per case on the basis of risk set sampling. All prescriptions of valproic acid and other antiepileptic drugs within 90 days (present users) or 91 to 365 days (past users) before hospital admission with acute pancreatitis, or index date among controls, were collected from the prescription databases in the counties. We performed conditional logistic regression to estimate the relative risk of acute pancreatitis after exposure to valproic acid or other antiepileptic drugs, adjusting for gallstone diseases, alcohol-related diseases, hyperlipidemia, and hypercalcemia. We included 3083 cases of acute pancreatitis and 30,830 population controls. The adjusted odds ratio (OR) for acute pancreatitis in present users of valproic acid was 1.9 [95% confidence interval (CI), 1.1-3.3); for past users, the adjusted OR was 2.6 (95% CI, 0.8-8.7). For users of other antiepileptic drugs, the corresponding adjusted ORs were 1.6 (95% CI, 1.2-2.2) and 1.8 (95% CI, 1.1-3.0). Use of valproic acid is associated with an elevated relative risk estimate for acute pancreatitis, but it was not materially different from past use or use of other antiepileptic drugs. Therefore, our data challenge the hypothesis that valproic acid is an independent risk factor for acute pancreatitis.

Incidence and risk for neutropenia/agranulocytosis among clozapine users: A retrospective cohort study.

Abstract Objective. To estimate the incidence and the risk of neutropenia or agranulocytosis (the outcome) associated with clozapine use (the exposure), and to identify risk factors. Methods. All data were derived from the computerized hospital database. Adult psychiatric patients were identified, and 95 incident clozapine users and 884 non-clozapine users were included. Cox proportional hazards regression was used to estimate the hazards ratio (HR) of developing the outcome after clozapine use adjusted for confounders. The interaction between clozapine and valproic acid was assessed a posteriori. Results. Throughout the 24-month follow-up, the incidence of neutropenia was 6.3% in the clozapine group and 5.8% in the non-clozapine group. One agranulocytosis was found in the non-clozapine group. The HR (95% CI) for neutropenia were: clozapine 1.33 (0.54–3.25) and age . 45 years 2.99 (1.63–5.48). Lithium, as an independent protective factor, reduced the risk for neutropenia by 85% compared with patients who did not receive lithium, HR 0.15 (95% CI 0.02–1.09). Valproic acid might potentiate the clozapine-associated neutropenia (HR 5.10, 95% CI 0.70–37.12). Conclusion. Clozapine might slightly increase the risk of neutropenia in psychiatric patients. Concerning clozapine-associated neutropenia, older patients are at increased risk and use of valproic acid concurrently with clozapine should be avoided.

Physicochemical properties, in vitro release and in vivo evaluation of tramadol hydrochloride rectal suppository and rectal gel

Abstract Background: Tramadol is a centrally acting analgesic drug. Rectal administration of tramadol is useful in the treatment of post-operative pain or malignant pain in cases where it cannot be administered orally. In Thailand, tramadol is available only as a capsule for oral use and as a solution for injection. Objective: Develop tramadol hydrochloride rectal suppositories and rectal gel preparations. Methods: Tramadol rectal suppository and rectal gel were prepared. Physicochemical properties (viscosity, gel strength, mucoadhesive force) and the in vitro release of tramadol hydrochloride were investigated from different bases (Witepsol H15, polyethylene glycol, poloxamer, and hydroxyethylcellulose). The analgesic activity of rectal tramadol hydrochloride using the hot plate test was evaluated in rats. Results: Tramadol hydrochloride rectal gel using poloxamer was more mucoadhesive to the rectal mucous membrane than was the gel with the hydroxyethylcellulose base. Tramadol hydrochloride was released rapidly in vitro from both the Witepsol H15 and polyethylene glycol bases. It was completely released from the polyethylene glycol suppository base within 15 minutes. The amount of tramadol hydrochloride release from the Witepsol H15 suppository base was about 93% at 120 minutes. When using poloxamer or hydroxyethylcellulose as a rectal base, tramadol hydrochloride was released from both bases rapidly and completely released within 15 minutes. Administration of a tramadol hydrochloride suppository in rats exhibited a more pronounced analgesic effect with the polyethylene glycol base than with the Witepsol H15-based suppositories. The rectal gel had a less pronounced analgesic effect when made with the hydroxyethylcellulose base than with the poloxamer base. Conclusion: Tramadol hydrochloride suppositories and rectal gels with different bases showed rapid and almost complete drug release from the bases, prolonging the latency of a nociceptive response in in vivo experiments.