Drug-drug interaction is a potential cause of adverse drug reactions. The incidence of such drug interactions in university hospitals in Thailand is unknown. To estimate the rate of potential drug-drug interactions in outpatients of a typical Thai university hospital, and to identify risk factors for such interactions in Thai patients. One-year outpatients' prescription data were retrieved from the hospital computer records. Potential drug interactions were identified using the existing drug-interaction database system. Potential interactions within a specific prescription and involving drugs prescribed 1-, 3- and 7-day earlier were searched for. Possible associations between occurrence of an interaction and a patient's age and gender and the number of items on the prescription were explored. The overall rate of potential drug interactions was 27.9% with a maximal value of 57.8% at the Department of Psychiatry. The rate of the most potentially significant interactions was 2.6%, being the highest in the Department of Medicine (6.0%), with isoniazid vs. rifampin as the most common interacting combination. The rate increased with the patient's age and prescription size (P=0.000). The odd's ratio of having at least one potential drug interaction was 1.8 (64.2%) when age increased by 20 years (P=0.000) and 2.8 (165.7%) when another drug was added (P=0.000). The rate of potential drug interactions was the same for both genders. The rate of potential drug interactions detected across prescriptions was higher than within prescriptions and was dependent on the time interval between prescriptions. Potential drug interactions were common in our sample of patients. The rate of such interactions increased with the number of drugs prescribed and the patient's age.
Detoxification and elimination of permethrin (PM) are mediated by hydrolysis via carboxylesterase (CES). Mitragyna speciosa (kratom) contains mitragynine (MG) and other bioactive alkaloids. Since PM and MG have the same catalytic site and M. speciosa is usually abused by adding other ingredients such as pyrethroid insecticides, the effects of MG and an alkaloid extract (AE) on the elimination of PM were investigated in rats. Rats were subjected to single and multiple pretreatment with MG and AE prior to receiving a single oral dose (460 mg/kg) of PM. Plasma concentrations of trans-PM and its metabolite phenoxybenzylalcohol (PBAlc) were measured. The elimination rate constant (kel) and the elimination half-life (t1/2 el) of PM were determined, as well as the metabolic ratio (PMR). A single and multiple oral pretreatment with MG and AE altered the plasma concentration-time courses of both trans-PM and PBAlc during 8–22 h, decreased the PMRs, delayed elimination of PM, but enhanced elimination of PBAlc. Results indicated that PM–MG or AE toxicokinetic interactions might have resulted from the MG and AE interfering with PM hydrolysis. The results obtained in rats suggest that in humans using kratom cocktails containing PM, there might be an increased risk of PM toxicity due to inhibition of PM metabolism and elimination.
1 December 2005 in Journal of Clinical Pharmacy and Therapeutics
A clinical event is likely to occur in patients receiving a pair of drugs, that have the potential to cause an interaction. The occurrence of a clinical drug-drug interaction in outpatients of university hospitals in Thailand is unknown. To investigate the occurrence of a clinical event associated with drug-drug interactions in outpatients at a Thai university hospital. A case-control study was established. The case was a sample group, randomly selected from a 1-year sample of outpatient prescriptions containing 'significance-1' potential drug-drug interactions, whereas the control was from the same year but with no potential drug interactions. Medical records of the cases and the controls were reviewed for an adverse event (AE) using a newly developed review form. The odds ratio of occurrence of the AE between the cases and the controls was determined. The AE was assessed for its possibility of being caused from a drug-drug interaction. The most common specific AE in both the cases and the controls was cough. An unplanned revisit to outpatient department or emergency room was found to be the most common general AE. The odds ratio of the occurrence of an AE in the cases, compared with the controls, was 1.495 (95% CI: 0.917-2.438). The possibility that the AEs resulted from drug interactions in the case group was nine 'probable' patients and 15 'possible' patients, whereas that in the control group was eight 'possible' patients. The most common interacting drug pair was isoniazid-rifampin with an increase in serum hepatic enzymes as the corresponding AE. Despite outpatients receiving drug pairs with a high potential for adverse interactions, the rate of occurrence of clinical drug interaction events was low.
5 February 2012 in Journal of Analytical Chemistry
A simple solid phase extraction method was developed for estimating the amounts of 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and methamphetamine (MA) in urine by using the GC-FID technique. The urine sample was alkalinized prior to undergoing solid phase extraction using Oasis HLB®. A 5% methanol-water mixture containing 2% ammonium hydroxide was used for washing, whereas a 70% methanol-water mixture containing 2% acetic acid was used for elution. The compounds were analyzed using the standard GC-FID conditions previously established for ecstasy samples, i.e., column: CP-SIL 24 CB WCOT (30 m × 0.32 mm i.d., 0.25 μm film thickness); carrier gas: N2 (2.6 mL/min); injector temperature: 290°C; detector temperature: 300°C; oven temperature: initial 80°C, final 270°C (1 min), ramp rate 20°C/min. Validation demonstrated the linearity of the calibration curves between 1 and 20 μg/mL (r > 0.99) for all analytes. The precisions (% RSD) were approximately 3–17%, 6–16% and 7–17% for MDMA, MDA and MA, respectively. The accuracies (% DEV) were (−)17-(+)5%, (−)18-(+)15% and (−)18-(+)0.6% for MDMA, MDA and MA, respectively. The recovery ranged from 80 to 107% and the lower limit of quantification (LLOQ) was 1 μg/mL. The method was successfully applied to determine the levels of these compounds in the urine of drug abuse suspects.
Betong watercress (Nasturtium officinale R.Br.) contains phenethyl isothiocyanate (PEITC), derived from myrosinase‐mediated hydrolysis of glucosinolates. Effects of fresh and cooked Betong watercress (FBW & CBW) on N‐demethylation and C‐8‐hydroxylation of caffeine (CF) in rats were investigated. Wistar rats received a single dose of CF before and after pretreatments with a single or five‐day administration of PEITC, FBW, and CBW dry powders. Plasma CF metabolic ratios (CMRs) were compared between before and after pretreatments. Single pretreatment with PEITC, FBW, but not CBW, significantly decreased CMRs. Five‐day pretreatment with PEITC, FBW, and CBW significantly decreased CMRs. The decreases in CMRs after multiple doses of PEITC, FBW, and CBW were significantly higher than after a single dose. The decrease in CMRs caused by CBW was significantly lower than those by FBW, both single‐ and multiple doses. Cooking decreases the activity of FBW in inhibition of CYP1A2 mediating CF metabolism. Practical applications PEITC and fresh watercress possess chemoprotective effects due to the inhibitory activity of PEITC on cytochrome P450s mediated bioactivation of carcinogens. Several clinical trials of the therapeutic uses of PEITC for cancer and other diseases are still in the pipeline. Betong watercress is a common ingredient in hot soup and stir‐fried Thai recipes. Cooking heat inactivates plant myrosinase involving the production of PEITC. Consumption of watercress in cooked form may contribute less chemoprotective benefit. More appropriate preparation to deliver PEITC is needed to be evaluated.