Saleh A. Bawazir

Liquid chromatographic determination of six antiepileptic drugs and two metabolites in microsamples of human plasma.

A simple, rapid, sensitive, and reproducible high-performance liquid chromatographic (HPLC) method for simultaneous determination of the antiepileptic drugs (ethosuximide, primidone, lamotrigine, phenobarbital, phenytoin, and carbamazepine) and two metabolites (carbamazepine-diol and carbamazepine-epoxide) in human plasma is described. The procedure involves extraction of the drugs from human plasma (100 microL) with ether using 9-hydroxymethyl-10-carbamyl acridan as an internal standard. The extract was evaporated and reconstituted with mobile phase and then injected onto the chromatograph. The drugs and the internal standard were eluted from a Supelcosil LC-18 stainless steel column at ambient temperature with a mobile phase consisting of a 0.01M phosphate buffer/methanol/acetonitrile (65/18/17, v/v/v) adjusted to a pH of 7.5 with phosphoric acid and a flow rate of 1 mL/min. The effluent was monitored at 220 nm. Quantitation was achieved by using peak area ratio of each drug to the internal standard. The intraassay and interassay coefficients of variation (CV) ranged from 2.43% to 6.25% and from 3.02% to 5.85%, respectively. The absolute (extraction) and relative (analytical) recoveries for the drugs ranged from 70.7% to 104.4% and from 88.3% to 106.1%, respectively. Stability tests showed that the drugs were stable in plasma for at least 4 weeks when stored at -20 degrees C. The method was applied clinically for monitoring the AEDs in epileptic patients.

A rapid liquid chromatographic method for the determination of lamotrigine in plasma

A rapid sensitive and simple high-performance liquid chromatographic (HPLC) method for the determination of lamotrigine in plasma is described. The drug was extracted from 100 microliters of plasma with chloroform:isopropanol (95:5% v/v) in the presence of 100 microliters of phosphate buffer (10 mM). The extract was evaporated and the residue was reconstituted with mobile phase and injected onto the HPLC system. The drug and the internal standard (chloramphenicol) were eluted from a Symmetry C18 stainless steel column at ambient temperature with a mobile phase consisting of 0.01 M potassium-acetonitrile-methanol (70.20:10% v/v/v), adjusted to pH 6.7, at a flow rate of 1.3 ml min-1 and the detector was monitored at 214 nm. Quantitation was achieved by measurement of the peak-area ratio of the drug to the internal standard and the lower limit of detection for lamotrigine in plasma was 20 ng ml-1. The intraday precision ranged from 3.34 to 6.12% coefficient of variation (CV) and the interday precision ranged from 2.15 to 8.34% CV. The absolute and relative recoveries of lamotrigine ranged from 86.93 to 90.71% and from 95.18 to 107.13%, respectively. The method was applied in studying the pharmacokinetics of lamotrigine administered orally to rabbits. This reliable micro-method would have application in pharmacokinetic studies of lamotrigine where only small sample sizes are available, e.g. paediatric patients.

Consumer attitudes towards community pharmacy services in Saudi Arabia

Objective The purpose of this study was to determine consumer attitudes towards community pharmacy and their preferences for the introduction of new services.

High-performance liquid chromatographic determination of furosemide in plasma and urine and its use in bioavailability studies.

A sensitive, selective and efficient reversed-phase high-performance liquid chromatographic (HPLC) method is reported for the determination of furosemide in human plasma and urine. The method has a sensitivity limit of 5 ng/ml in plasma, with acceptable within- and between-day reproducibilities and good linearity (r2>0.99) over a concentration range from 0.05 to 2.00 microg/ml. The one-step extract of furosemide and the internal standard (warfarin) from acidified plasma or urine was eluted through a muBondapak C18 column with a mobile phase composed of 0.01 M potassium dihydrogenphosphate and acetonitrile (62:38, v/v) adjusted to pH 3.0. Within-day coefficients of variation (C.V.s) ranged from 1.08 to 8.63% for plasma and from 2.52 to 3.10% for urine, whereas between-day C.V.s ranged from 4.25 to 10.77% for plasma and from 5.15 to 6.81% for urine at three different concentrations. The minimum quantifiable concentration of furosemide was determined to be 5 ng/ml. The HPLC method described has the capability of rapid and reproducible measurement of low levels of furosemide in small amounts of plasma and urine. This method was utilized in bioavailability/pharmacokinetic studies for the routine monitoring of furosemide levels in adults, children and neonate patients.

High performance liquid chromatographic determination of ranitidine in human plasma

Abstract A rapid reversed phase HPLC method for determination of ranitidine in human plasma has been developed. The procedure involved extraction of the drug from alkalinized plasma spiked with the internal standard (procainamide) using 4% v/v isopropanol in ethylacetate. The extract was evaporated under nitrogen and the residue was reconstituted with methanol and injected onto U-Bondapak C18 column. The mobile phase is 8% v/v acetonitrile in 10 mM potassium phosphate buffer (pH 5.1); at a flow rate of 2.5 ml/min and UV detection at 330 nm. The efficiency of extraction was 90% with a detection limit of 20 ng/ml. The within-day coefficient of variations ranged from 4.09% to 5.81%, whereas those of between-day were from 7.5% to 9.51%.

Comparative Study of Saudi-Marketed Products and US Drug Labeling

Drug package inserts from ten nonsteroidal antiinflammatory drugs marketed in Saudi Arabia were compared with their corresponding US labels to determine possible differences in their information content. These variations were assessed with special regard to the number of words used and the type of the information provided. The study showed that inserts of Saudi-marketed products generally conveyed limited and incomplete information. Possible adverse reactions, drug-drug interactions, and date of revision often were not included, although this information was present on the corresponding US labels. Comparisons of the package inserts of the same product from various pharmaceutical companies show wide variations in the amount of information provided. Determining the minimal level of information that must be included by the manufacturer in the package insert and the establishment of firm international guidelines by the World Health Organization could effectively reduce such variations.

Effects of Pregnancy on the Pharmacokinetics of Lamotrigine in Dogs

Summary: Purpose: This study was designed to evaluate the effects of pregnancy on the kinetics of lamotrigine (LTG).

Public Attitude toward Drug Technical Package Inserts in Saudi Arabia

Objective: To examine public opinion in Saudi Arabia regarding the technical drug package insert (PI) as a source of information and to assess the need for potential changes to the existing format in favor of a more patient-oriented package insert (PPI). Design: A cross-sectional survey was conducted from March through May 1998 by means of a self-administered questionnaire. Setting: Eighty-four community pharmacies in Riyadh. Participants: Two thousand twenty-nine customers entering community pharmacies in Riyadh were enrolled in this survey. Results: Results of the survey showed that 88% of the respondents read the PI. The motives for reading the PI included the desire to know more about the medication (48.7%), to adhere to the prescription (21.7%), and to decide whether to take the medication (13.1%). From the list of information contained therein, respondents listed indications (47.1%) and adverse drug effects (46.6%) as the principal sections of interest. Respondents overwhelmingly endorsed the PI as a complementary source of drug information to the verbal instructions of the physician and the pharmacist. However, readers did criticize its detail, legibility, and poor graphic illustration. Respondents indicated their desire to see a concise PPI introduced, one that highlights only the most common adverse effects of a drug. It should be written in simple Arabic and include, whenever possible, illustrations to enhance comprehension. Conclusions: The PI does not have the power to overrule the physicians or pharmacists instructions. Since some patients may cease taking their medicines if they feel threatened by the adverse effects mentioned in the PI, precautionary statements should be prominently placed in the PI to explain the purpose of mentioning such information and what proper action should be taken by the patient.

Effect of valproic acid on the pharmacokinetic profile of oxcarbazepine in the rat

The pharmacokinetics of oxcarbazepine (30 mg kg-1, po), administered for 1 week, was studied in rats pre-treated for 2 weeks with valproic acid (100 mg kg-1, po). Oxcarbazepine (OXC) plasma levels were measured over a period of 24 h from dosing, using a sensitive HPLC method. No significant changes were observed in the mean values of OXC pharmacokinetic parameters (Cmax, Tmax, t1/2 and AUC0-infinity) between the control and the pre-treated groups. The findings of this study suggest that OXC metabolism in the rat is apparently not affected by valproic acid, and the lack of effect may be attributed to the different pathways of biotransformation of the two drugs.

The interaction potential of vigabatrin with phenytoin and carbamazepine

Abstract The effect of vigabatrin on the pharmacokinetic profiles of orally coadministered doses of phenytoin (PT) and carbamazepine (CBZ) was examined in the rat. Plasma PT and CBZ levels were serially monitored over a 24 h period using an HPLC technique. Coadministration of vigabatrin markedly delayed drug absorption (i.e., longer T max ) and significantly reduced the plasma levels of PT and CBZ as assessed by the depression in the respective AUCs. These corresponded to a reduction of 21 and 17%, respectively. The effect on plasma drug concentration was not paralleled by any significant change in the elimination half-lives (t 1 2 ) of the drugs. The similarity in the pattern and magnitude of interaction observed with both drugs suggests a common underlying mechanism. In the absence of hepatic factors, and with vigabatrins negligible influence on plasma protein binding, gastrokinetic property for vigabatrin is proposed as a likely mechanism to account for the interactions, but clearly further studies are needed to firmly establish this drug action.