Population pharmacokinetics of gentamicin in acute lymphoblastic leukemia pediatric patients compared to non-oncology patients.

Understanding the pharmacokinetics of gentamicin is essential in special populations, such as pediatric patients with acute lymphoblastic leukemia (ALL), in light of previous studies indicating that ALL patients have a lower volume of distribution than non-ALL patients. Furthermore, validation of such results is needed to ensure their clinical application. Accordingly, this single-center, retrospective, cross-sectional study compares the pharmacokinetic parameters of volume of distribution and clearance (Cl) of gentamicin between ALL and non-ALL patients. Inclusion criteria were pediatric patients aged between 1 and 14 years with or without ALL and receiving intravenous gentamicin for treatment courses > 72 h. Patients' characteristics, such as age, sex, height, serum albumin, diagnosis, serum creatinine (Scr) concentration, dosing, and pharmacokinetic information, including peak and trough concentrations, were retrieved. The study scrutinized a total of 115 pediatric patients, comprising toddlers (15.7 %), children (76.5 %), and adolescents (7.8 %). All patients received gentamicin every 8 h, with an average dose of 2.50 (0.64) mg/kg. Patients were divided into two groups based on disease state, with 45.2 % (n = 52) in the non-ALL group and 54.8 % (n = 63) in the ALL group. Both groups had similar characteristics in terms of gender, weight, body surface area, and dose. The only significant covariates identified were weight and creatinine clearance (Clcr) for volume of distribution (Vd). A significant difference was found in Scr, Clcr, and blood urea nitrogen (BUN); however, no significant difference between ALL and non-ALL patients emerged in the volume of distribution or Cl. In conclusion, the study findings indicate that dosing requirements were similar between the two groups. Further prospective studies with larger sample sizes are warranted.

Pharmacokinetic profile of sildenafil citrate in healthy Middle Eastern Males: Comparison with other ethnicities.

AIM: 1) To investigate the pharmacokinetic profile of sildenafil citrate in Middle Eastern males and, 2) To highlight the impact of ethnicity on its pharmacokinetics parameters through comparing Middle Eastern data to the data estimated from different ethnic groups. METHOD: The study was conducted on 24 Middle Eastern healthy male volunteers. Pharmacokinetic data including Cmax, Tmax, t1/2, AUC0-t, AUC0-∞ were estimated from blood samples collected at several time points within 24 h post-administration of a single 100-mg tablet of sildenafil citrate (Viagra®). Pharmacokinetic data of sildenafil generic 100-mg tablet (product B) was determined in the volunteers using the same analytical method. Pharmacokinetic data of other studies published on different ethnicities were obtained and compared to our Viagra®-related data. RESULTS: Analysis of Middle Eastern data (mean ± SD) revealed Cmax = 398.9 ± 107.7 ng/ml; Tmax = 1.84 ± 0.22 h; t1/2 = 2.66 ± 0.97 h; AUC0-24 = 1475 ± 515.3 ng.h/ml; AUC0-∞ = 1556 ± 567.58 ng.h/ml. There was no significant difference between Viagra® and product B, confirming the bioequivalence of the two preparation as well as the reliability of utilized analytical method. Data comparisons between Middle Eastern and other ethnicities indicated that Iranian, Mexican, and Thai would potentially have twice the effect observed in Arabs and Caucasians, considering the same prescribed drug formulation and dose. CONCLUSION: There is a considerable difference in the pharmacokinetic profile of sildenafil citrate between Middle Eastern and other ethnic groups. Ethnicity may predispose individuals to unwanted prolonged activity of sildenafil and adverse events. Thus, it should be taken in consideration by clinicians when recommending sildenafil dose.

A National Survey of Attitudes and Practices of Physicians Relating to Therapeutic Drug Monitoring and Clinical Pharmacokinetic Service: Strategies for Enhancing Patient's Care in Saudi Arabia.

PURPOSE: The aim of the study was to evaluate physicians' perception of the concept of pharmacokinetics and therapeutic drug monitoring (PK/TDM) and their use in clinical practice. METHODS: A novel, structured, self-administered questionnaire was designed, validated and distributed to physicians in 3 major cities in Saudi Arabia (Riyadh, Jeddah, Dammam) during a 4-month period. Data were collected on demographics, knowledge and practice of PK/TDM. Attitudes toward integrating these skills into daily clinical practice were also investigated. RESULTS: A total of 724 physicians completed the survey and included in the study. European and North American physicians were found to be more exposed to PK/TDM than other physicians. About 70% of the participants stated that they have applied PK/TDM in their practice, at least, once and most of these were consultants. Only 4.3% of respondents had never checked organ function prior to prescribing narrow therapeutic index drugs. Although the majority (78.4%) perceived PK/TDM as very important to their practice, only 35.3% have tried to calculate drug PK parameters for their patients when necessary. CONCLUSION: The result of this study showed that the knowledge of physicians about PK/TDM was inadequate. Moreover, the utilization of competent clinical pharmacists trained in PK/TDM was low. An interdisciplinary educational program between the physicians and pharmacist in PK/TDM will lead to a better health care outcome.

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

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.

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

OBJECTIVE: To assess the drug information-seeking behavior of physicians in Saudi Arabia and the information resources they were using to obtain information about new drugs. The physicians' awareness of the existence of drug information centers (DICs) and their attitudes toward these centers were also investigated. Physicians were also surveyed concerning their future information needs. METHODS: The study was conducted between September 2002 and June 2003. A questionnaire was sent to 2,000 registered physicians. Data were collected on demographics, drug information resources currently used by physicians, attitudes towards DICs and future information needs. RESULTS: Response rate was 65.9%. Only 70% of the physicians were aware of the existence of DICs in KSA and 33.9% have used this service before with request rate of 0.3/month during the last 6 months prior to survey. Physicians relied heavily on books (79%), periodicals (59.2%), symposia (55.1%) and pharmacists (35.3%). Physicians searched for information 17.5 times during the last 6 months and only 57.3% were using computers and 40% had no access to the Internet at work. CONCLUSION: Physicians in KSA had passive attitudes toward DICs. These centers are under-utilized by health care professionals, in part due to the lack of awareness of their existence by physicians. Drug newsletters and continuing education programs in information-retrieval and evaluation based on evidence-based medicine techniques to promote DIC's services should be instituted.

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

Abouthiouzine is a newly synthesized antithyroid agent with a proposed less adverse effects profile than other currently used drugs. A simple and rapid reversed phase high performance liquid chromatography assay was developed to determine the concentration of abouthiouzine in human plasma. The procedure involved extraction of the drug and propranolol (internal standard) from the plasma using ethylacetate. The extract was evaporated under nitrogen and the residue was constituted with the mobile phase and injected onto micro-Bondapack phenyl column (10 microm, 3.9 mm x 150 mm). The mobile phase consisted of 10 mM potassium dihydrogen phosphate buffer, acetonitrile, and methanol in the ratio of 60:25:15 (v/v/v, pH=3.0), which was delivered at a rate of 1.5 ml/min. Abouthiouzine and the internal standard were monitored using UV detection at 240 nm; the run time was less than 5 min. The detection limit of abouthiouzine is 0.5 microg/ml. The within- and between-day coefficients of variation were less than 7%. Our method has been successfully used to measure abouthiouzine plasma concentrations in a rabbit model following an intravenous administration of the drug.

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

Pharmacokinetic interaction of ketoconazole and itraconazole with ciprofloxacin.

The effect of the concomitant administration of the antifungal drugs ketoconazole (KTC) and itraconazole (ITC) on the pharmacokinetics of ciprofloxacin (CIP) following short- and long-term administration in mice was investigated. Animals received either a dose of CIP (20 mg/kg, i.p.), CIP (20 mg/kg, i.p.) together with KTC (50 mg/kg, p.o.) or CIP (20 mg/kg, i.p.) and ITC (30 mg/kg, p.o.). The same treatments were repeated for 7 days. Blood samples were collected up to 4 h following drug administration and two urine samples were collected at 2 h and 4 h after drug administration. CIP plasma concentrations were significantly higher in KTC- and ITC-treated groups compared with the corresponding control groups. The concomitant administration of KTC or ITC with CIP also significantly (p<0.05) increased C(max), t(1/2), MRT and AUC(0-infinity) with no change in T(max). CIP clearance was significantly reduced by both agents. KTC and ITC reduced CIP urinary excretion. This study suggests that an important pharmacokinetic interaction between CIP and KTC or ITC is likely to occur when either of the two antifungal drugs is administered concomitantly with CIP. The results may suggest possible reductions in total clearance of CIP, owing to inhibition of its renal tubular excretion by KTC and ITC.

Disposition of abouthiouzine: a novel antihyperthyroid drug.

Abouthiouzine is a novel antithyroid agent with a profile of fewer reported adverse effects than other currently used drugs. The purpose of this current work was to explore, for the first time, the disposition of abouthiouzine following intravenous and oral administration using an animal model; also, to study its plasma protein binding properties. Abouthiouzine (2 mg/kg intravenously) was administered to healthy male Vole rabbits and Beagle dogs. A dose of 20 mg/kg of the drug was also given orally to another group of Beagle dogs. Abouthiouzine plasma concentrations were measured using an HPLC method, and its pharmacokinetic parameters were determined by non-compartmental analysis. Abouthiouzine plasma protein binding was determined using an ultrafiltration technique. The drug was quickly eliminated from the rabbit and dog systemic circulations with terminal half-lives (T(1/2 lambda)) of 0.7 h and 1.9 h, respectively. The calculated T(1/2 lambda) following the oral administration in dogs was 1.8 h. Total abouthiouzine clearance (CL) in rabbits was 7.84+/-0.87 ml/min/kg, and 4.03+/-0.83 ml/min/kg in dogs. The apparent volume of distribution at steady state (V(ss)) in rabbits and dogs was 360.09+/-63.41 ml/kg and 481.10+/-62.64 ml/kg, respectively. The absolute oral bioavailability in dogs was approximately 16%, which may indicate poor absorption characteristics of the pure drug and/or an extensive first past effect. Protein binding studies have demonstrated that abouthiouzine has moderate-to-high binding properties ( approximately 63%-86%). Further studies are needed to evaluate the route of elimination of abouthiouzine in these animal models including any metabolite formation and the role of enterohepatic recycling in this process.