Tablet splitting and weight uniformity of half-tablets of 4 medications in pharmacy practice.

BACKGROUND: Tablet splitting is a common practice for multiple reasons including cost savings; however, it does not necessarily result in weight-uniform half-tablets. OBJECTIVES: To determine weight uniformity of half-tablets resulting from splitting 4 products available in the Jordanian market and investigate the effect of tablet characteristics on weight uniformity of half-tablets. METHODS: Ten random tablets each of warfarin 5 mg, digoxin 0.25 mg, phenobarbital 30 mg, and prednisolone 5 mg were weighed and split by 6 PharmD students using a knife. The resulting half-tablets were weighed and evaluated for weight uniformity. Other relevant physical characteristics of the 4 products were measured. RESULTS: The average tablet hardness of the sampled tablets ranged from 40.3 N to 68.9 N. Digoxin, phenobarbital, and prednisolone half-tablets failed the weight uniformity test; however, warfarin half-tablets passed. Digoxin, warfarin, and phenobarbital tablets had a score line and warfarin tablets had the deepest score line of 0.81 mm. CONCLUSION: Splitting warfarin tablets produces weight-uniform half-tablets that may possibly be attributed to the hardness and the presence of a deep score line. Digoxin, phenobarbital, and prednisolone tablet splitting produces highly weight variable half-tablets. This can be of clinical significance in the case of the narrow therapeutic index medication digoxin.

Availability and costs of antiepileptic drugs and quality of phenobarbital in Vientiane municipality, Lao PDR.

PURPOSE: In developing countries, availability and quality of drugs are critical factors for effective management and control of epilepsy. This study investigated the availability and costs of antiepileptic drugs (AEDs), and the quality of phenobarbital in Vientiane Municipality, Lao PDR. METHODS: In March 2004, we enrolled all pharmacies (categories I and II) of four central districts of Vientiane eligible to sell AEDs. Two hundred and eight pharmacies of category III (75.1% of all registered pharmacies) were excluded as the sale of AEDs was not authorized. All pharmacists were interviewed with a standard questionnaire. Whenever phenobarbital was available, a sample was purchased and assayed by liquid chromatography. Phenobarbital was defined as being of correct quality if the active substance average content corresponded to +/-15% of the indicated amount. RESULTS: 66 pharmacies were enrolled (13 and 45 of categories I and II, respectively, and 8 hospital pharmacies). Six generics of AEDs were found (phenobarbital, phenytoin, valproic acid, clonazepam, carbamazepine, diazepam) and all pharmacies sold at least 1 AED. The 2 most widely available drugs were diazepam (5 mg) and phenobarbital (100 mg), present in 87.9 and 53.0% of the pharmacies, respectively. All 34 phenobarbital samples examined showed a correct concentration of the active compound. However, the concentration of phenobarbital 100 mg tablets produced in Lao PDR (mean concentration 94.7 mg) was significantly lower (p = 0.005) than the imported equivalent (mean concentration 99.7 mg). The direct drug costs of a yearly treatment with phenobarbital were estimated to be at least 25.2 USD. CONCLUSIONS: A variety of AEDs are present. Their availability, particularly of phenobarbital, is restricted to higher-category pharmacies and within those it is rather limited. To meet the costs of AEDs in this setting is a major challenge for people with epilepsy. However, the quality of the available phenobarbital was rather satisfactory.

Quality of phenobarbital solid-dosage forms in the urban community of Nouakchott (Mauritania).

PURPOSE: Epilepsy is a major public-health problem in Africa. The quality of available drugs is a limiting factor for an adequate management. The aim of this study was to describe the proportion of poor-quality phenobarbital (PB) solid-dosage forms and evaluate the factors associated with its quality in Nouakchott (Mauritania). METHODS: A cross-sectional study was carried out within pharmacies, hospitals, and on the parallel market in March 2003. PB samples were bought by a native person and then assayed by a liquid chromatography method. A package was considered to be of good quality if the active-substance average content was between 85 and 115% of the stated content printed on the packet. RESULTS: Forty-five pharmaceutical stores were visited, enabling us to collect 146 samples of PB. Three brand names were available in Nouakchott. They originated from France, Morocco, Senegal, and Egypt. Results: A prevalence of 13.7%[95% confidence interval (CI), 8.8-20.0] of poor-quality PB was found. All samples from Morocco were underdosed. The generic active content was satisfactory, but saccharose, an excipient with a potential side effects, was identified. Two factors associated with the good quality of PB have been put forward: tablets manufactured in France and loose packaging as generics conditioned in such a way were of good quality. CONCLUSIONS: This study shows that the quality of antiepileptic drugs in Africa is still worrying. The setting up of medicine quality control in Mauritania is legitimate. Considering the good quality of generic PB and its lower cost, this type of medicine should be promoted in this region.

Validation of a quick modeling program generating clearance estimates at steady state for routine therapeutic drug monitoring.

Therapeutic drug monitoring (TDM) of chronic treatments is justified for several reasons, including relative over- or underdosage due to variable individual elimination, pharmacokinetic interactions in drug combinations, and noncompliance. In all these circumstances, the prescribing physician is interested in having an estimation of the patient's clearance of the drug, even from one measurement. We compare a validated bayesian program, USC*Pack of Jelliffe, found difficult to use in daily routine, with a "home-made" program. The latter, which is capable of taking data from a clinical database, will generate a graphic simulation of daily plasma drug concentrations together with an estimation of steady-state clearance more rapidly than does USC*Pack. Both programs were run with only one measured plasma level. The patients were 83 children or young adults treated with phenobarbital (PB), carbamazepine (CBZ), and/or Valproic acid (VPA) who were resistant to monotherapy and who were to be sampled two to four times between doses. Drugs were routinely assayed by high-performance liquid chromatography (HPLC). Despite the rough character of Phacile (numeric integration and adjustment of only two of three parameters, without an acknowledged minimization algorithm), the results are comparable to those obtained with USC*Pack for estimating clearance and predicting plasma drug concentrations. Phacile algorithm, although simple, has proven of interest in routine TDM and as an introduction for medical students to the bayesian approach of population pharmacokinetics.

Safety of a higher loading dose of phenobarbital in the term newborn.

The conventional loading dose of phenobarbital for newborn infants with hypoxic-ischemic seizures, 20 mg/kg, often fails to control convulsive activity. To determine the safety of a higher loading dose and to establish the pharmacokinetic parameters of a higher loading dose, ten severely asphyxiated term newborns were given 30 mg/kg of phenobarbital intravenously over 15 minutes. The mean serum concentration of phenobarbital two hours after loading was 30.0 +/- 3.2 micrograms/mL, the apparent volume of distribution was 0.97 +/- 0.18 L/kg, total clearance was 0.08 +/- 0.03 mL/min/kg, and mean serum half-life was 148 +/- 55 hours. The higher loading dose was not associated with any short-term adverse effects on cardiorespiratory function, even in spontaneously breathing infants.