Hisham S. Abou-Auda

An economic assessment of the extent of medication use and wastage among families in Saudi Arabia and Arabian Gulf countries

BACKGROUND Expenditures for prescription and over-the-counter medications constitute a large percentage of total health care costs. Governments, health care providers, and consumers must work together to find ways to control these costs while continuing to provide quality health care for their nations. To this end, medication wastage is an unnecessary burden on an already fiscally restrained health care system. OBJECTIVE This study was conducted to identify the extent of medication use and wastage among families in the Arabian Gulf countries, with an emphasis on Saudi Arabia. METHODS A questionnaire was developed and administered to households in 5 regions in Saudi Arabia and other Gulf countries. A total of 1641 households participated in the study (1554 in Saudi Arabia; 87 in other countries). RESULTS The mean (SD) family size of household respondents from Saudi Arabia was 6.60 (3.20) members, with 0.32% reporting no medicines present in the household, 81.8% of households reporting 5 or more medicines, and 29.9% of respondents reporting having at least 10 medications at home. Overall, the mean (SD) number of medicines per household in Saudi Arabia was 8.0 (4.3). The most common therapeutic classes of medications kept at home in Saudi Arabia were respiratory medications (16.8%), central nervous system agents (16.4%), and antibiotics (14.3%). The mean (SD) number of drug products unused, deteriorated, or expired was 2.2 (2.7) and 2.7 (1.9) per household in Saudi Arabia and other Gulf countries, respectively. From these data, mean medication wastage was estimated to be 25.8% (Saudi Arabia) and 41.3% (other Gulf countries). When analyzed on the basis of total medication cost, medication wastage was 19.2% and 25.0% in Saudi Arabia and other Gulf countries, respectively. The mean out-of-pocket expenditure (based on the percentage of annual income) for medications was 0.72% for households in Saudi Arabia compared with 0.48% in other Gulf countries. CONCLUSIONS Families in Saudi Arabia and other Gulf countries spent a total of approximately US

Liquid chromatographic assay of nifedipine in human plasma and its application to pharmacokinetic studies.

150 million on medications that were never consumed. However, there appear to be no immediate solutions to the problem of medication wastages impact on health care costs. The use of generic alternatives should be promoted, and drug use assessments should be implemented on a national level.

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

A highly sensitive, selective and reproducible reversed-phase high-performance liquid chromatographic method has been developed for the determination of nifedipine in human plasma with minimum sample preparation. The method is sensitive to 3 ng/ml in plasma, with acceptable within- and between-day reproducibilities and linearity (r2 > 0.99) over a concentration range from 10-200 ng/ml. Acidified plasma samples were extracted using diethyether containing diazepam as internal standard and chromatographic separation was accomplished on C18 column using a mobile phase consisting of acetonitrile, methanol and water (35:17:48, v/v). The within-day precision ranged from 2.22 to 4.64% and accuracy ranged from 102.4-106.4%. The day-to-day precision ranged from 2.34-7.07% and accuracy from 95.1-100.1%. The relative recoveries of nifedipine from plasma ranged from 91.0-107.3% whereas extraction recoveries were 88.6-93.3%. Following eight 6-week freeze-thaw cycles, nifedipine in plasma samples proved to be stable with accuracy ranging from 0.64 to 3.0% and precision ranging from 3.6 to 4.15%. Nifedipine was also found to be photostable for at least 120 min in plasma, 30 min in blood and for 60 min in aqueous solutions after exposure to light. The method is sensitive and reliable for pharmacokinetic studies and therapeutic drug monitoring of nifedipine in humans after the oral administration of immediate-release capsules and sustained-release tablets to five healthy subjects.

Influence of piperacillin on the pharmacokinetics of methotrexate and 7-hydroxymethotrexate

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.

Atom level electrotopological state indexes in QSAR: designing and testing antithyroid agents.

Abstract The influence of concomitant administration of piperacillin (PIP) on the pharmacokinetic parameters of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH-MTX) was studied in rabbits. Six rabbits received an initial i.v. bolus (0.21 mg kg−1) followed by a constant-rate i.v. infusion of the drug (5 μg min−1 kg−1) for 240 min. The PIP dose (30 mg kg−1) was repeated every 30 min until the end of the infusion period. The control group consisted of four rabbits treated the same way except for the addition of PIP. There were significant increases in the mean residence times found for MTX (MRTinf) and 7-OH-MTX (MRTm,inf) following PIP administration. Concomitant administration of PIP with MTX also produced significant 1.5- and 2.8-fold increases in the area under the curve of MTX and 7-OH-MTX, respectively. The total body clearance of MTX and the operative total body clearance of 7-OH-MTX significantly decreased, but in a less than proportional manner. The study demonstrates that the interaction between MTX and PIP is mainly due to the reduced clearance of both MTX and 7-OH-MTX combined with a slight increase in the formation clearance of the metabolite.

A new accurate method for predicting lithium clearance and daily dosage requirements in adult psychiatric patients.

AbstractPurpose. To design new antithyroid agents with less side effects, the electrotopological-state (E-state) indexes of thiourylene moiety (SN&S) was utilized as a guideline to develop five acyclic thio-urylene-type compounds with reduced antioxidant property. Methods. These agents were synthesized and screened for antithyroid activity in rats using 125I-thiocyanate discharge technique. In addition, chemiluminescence studies on the activated polymorpho-nuclear leukocytes (PMNLs) were also conducted to reveal antioxidant properties of the tested compounds. Results. A linear relationship between the in vitro literature value of the formation constants of thiourylene-type compounds with iodine (Kc) and the SN&S was observed and utilized in designing those agents. At least one of the compounds (abouthiouzine) was found to have a potential value as an antithyroid agent. The relative efficacy of abouthiouzine [l-n-butyl-3(isonicotinamido)-2-thiourea], after equimolar dose, was 102% and 51.5% of that of propylthiouracil with respect to the rate of 125I-discharge and 125I-uptake, respectively. In addition, Chemiluminescence studies on PMNLs revealed that abouthiouzine has slight oxidant property. Such properties may provide advantages in avoiding the iatrogenic hypothyroidism and antithyroid-induced immunological reactions. Conclusions. The E-state approach provides guidelines to economize efforts and cost of designing new antithyroid drugs.

Comparative Study of Saudi-Marketed Products and US Drug Labeling

OBJECTIVE The present study aimed to derive new equations for estimating lithium clearance and daily dosage requirements needed to achieve an intended lithium serum level for adult psychiatric inpatients and outpatients. METHODS Data were retrospectively collected from 60 adult psychiatric patients (34 males and 26 females, aged between 18-80 years) in both inpatient and outpatient settings. All variables that might affect lithium clearance and/or lithium serum concentration were included and analyzed by stepwise multiple linear regression to produce equations describing lithium clearance and daily dosage requirements for these patients. The validation of the developed equations was performed by application to another 60 psychiatric subjects in both the inpatient and outpatient settings. The bias and accuracy of the new methods were also compared to those set forth by the empirical method and the a priori methods developed by Zetin, Pepin, Jermain and Terao and colleagues. RESULTS The following prediction equations for lithium clearance (CL(Li)) were obtained: CL(Li) (inpatients) = 0.932 + 0.185CL(Cr) and CL(Li) (outpatients) = 1.021 + 0.141CL(Cr). The equations derived for daily dosage requirements were: daily dose (inpatients, mg) = 350.15 + 289.92 (desired lithium level, mmol/L) + 0.84 (weight, kg) - 1.76 (age, years) + 34.43 [tricyclic antidepressant (TCA), yes = 1, no = 0] + 62.1(CL(Cr), L/h) + 13.1 [blood urea nitrogen (BUN), mmol/L] + 40.9 (sex, male = 1, female = 0) and daily dose (outpatients, mg) = 784.92 + 530.22 (desired lithium level, mmol/L) + 8.61 (weight, kg) - 12.09 (age, years) - 11.14 (TCA, yes = 1, no = 0) - 7.63 (CL(Cr), L/h) - 42.62 (BUN, mmol/L) - 23.43 (sex, male = 1, female = 0). In the present method, the prediction error for clearance was 10.31% and 6.62% for inpatients and outpatients, respectively, and the prediction error for daily dosage requirements was 3.96% and 2.95% for inpatients and outpatients, respectively. CONCLUSIONS Compared to previously reported methods, the present method proved to be accurate and can be safely used for the prediction of lithium clearance and daily dosage requirements in psychiatric inpatients and outpatients.

Public Attitude toward Drug Technical Package Inserts in Saudi Arabia

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.

Formulation and pharmacokinetics of multi-layered matrix tablets: Biphasic delivery of diclofenac

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.

Information-seeking behaviors and attitudes of physicians toward drug information centers in Saudi Arabia

The rapid availability of the drug at the site of action followed by maintaining its effect for a long period of time is of great clinical importance. Thus, the purpose of the present study was to prepare and evaluate multi-layered matrix tablets of diclofenac using Eudragit RL/RS blend to achieve both immediate and sustained therapeutic effects. Diclofenac potassium (25 mg) was incorporated in an outer immediate release layer to provide immediate pain relief whereas diclofenac sodium (75 mg) was incorporated in the inner core to provide extended drug release. Wet granulation was employed to prepare the inner core of the tablets that were further layered with an immediate release drug layer in the perforated pan coater. The in-vitro and in-vivo performance of the developed formulation was compared with the marketed products Voltaren® SR 75 mg and Cataflam® 25 mg. The in-vitro drug release of the prepared formulation showed similarity (f2 = 66.19) to the marketed product. The pharmacokinetic study showed no significant difference (p > 0.05) in AUC0-24 and Cmax between the test and reference formulations. The AUC0-24 values were 105.36 ± 83.3 and 92.87 ± 55.53 μg h/ml whereas the Cmax values were 11.25 ± 6.87 and 12.97 ± 8.45 μg/ml, for the test and reference, respectively. The multi-layered tablets were proved to be bioequivalent with the commercially available tablets and were in agreement with the observed in-vitro drug release results. Stable physical characteristics and drug release profiles were observed in both long term and accelerated conditions stability studies.