Co-prescribed Drugs Research Articles

Imprudent Gastro-protective Approach in Majority of Specialists' Clinics of a Tertiary Hospital.

One out of four prescriptions in out-patient departments contains a gastro-protective drug (APUD) - PPI/ H2 Blockers/ Antacids/ Ulcer Protective's. These drugs should be prescribed only when there is a justified indication. To assess the prescriptions of gastro-protective agents for appropriateness and rationality, in a tertiary care hospital setup. It was a cross-sectional observational study conducted from Aug 2013 to Dec 2013 at OPDs of a Tertiary Care Teaching Hospital, Pune. A total of 260 prescriptions containing gastro-protective agents were analysed for appropriateness and rationality. Rationality of drug use was assessed by referring to standard textbooks and guidelines. Cost difference data was analysed by Wilcoxon signed rank test using GraphPad Prism 6. Most common class of gastro-protective agents was Proton pump inhibitors (PPIs)-73.77% (Pantoprazole & Dexrabeprazole). Only 37.3% prescriptions had an adequate indication for these drugs {GI prophylaxis (29.6%) and Acid Peptic Disease treatment (7.7%)}. Two irrational Fixed dose combinations found in the study were PPI with prokinetic agent (n=65) and Proton Pump Inhibitor + NSAID combination (n=2). Formulation, spelling and strength errors were found with 75 prescribed drugs. Medication instructions were lacking with most of the drugs. Drug interactions with co-prescribed drugs could be anticipated in 79 cases. Injudicious use of anti-peptic ulcer agents significantly increased the cost of prescriptions (p<0.0001). Anti-ulcer drugs are overenthusiastically prescribed by all specialties which can predispose to adverse effects, drug interactions, increased cost and even erroneous prescriptions.

0213: Prolongation of the QT interval under antipsychotics in the Moroccan patient

The cardiovascular mortality of the psychiatric patients is higher than the general population. The antipsychotics and their propriety of prolongation of the QT interval seems to be a possible track. We tried to analyze the epidemiological, clinical, biological, therapeutic and especially electrocardiographic (ECG) data in those patients, to determine the prevalence of the syndrome of prolongation of the QT interval and investigate its main risk factors. We conducted a cross-sectional study, at the university psychiatric center Ibn Rochd of Casablanca, in collaboration with the cardiology department, over one year, concerning 134 patients receiving an antipsychotic treatment, we realized12 derivations ECG, and assessed clinical, biological and pharmacological data. The mean age was 32, 48±10,9 year,82,8% men/17,2% women, the first psychiatric disorder was the paranoid schizophrenia 56%, hyperkalemia was present in1 patient, hyermagnesaemia (1), calcemia was normal, polytherapy has been found in the majority of cases(2.8±0.9), neuroleptics were prescribed for all patients(45.5% for long term), in association with benzodiazepines (25%) and anticholinergics (23%), antidepressant (21%) and lithium (10%).The mean dose antipsychotic chlorpromazine equivalent (CPZ eq) is 617.8±534, 3mg/d, 88% of patients are under moderate doses and only 6% receive very high doses >2000mg/d CPZ eq. the mean heart rate was 82.7±16.5 BPM, one patient had a bradycardia to 44 bpm. The mean QTc is 386.22±30,9ms, the prevalence of long QT syndrome (>440ms) in our series is 4.5% so lower than the literature. The mean value of QTc increases with age, and it is higher in female gender, the risk of QT prolongation is associated with multiple co-prescribed drugs, and gets higher with the number of prescribed drugs and with strong dosage. The risk increases also at the beginning of the treatment and in patients with long term treatment >6 months. However, despite the proven toxicity of these treatments, it must be remembered that the QT prolongation does not necessarily induce a negative risk-benefit balance. This is to be assessed on a case-by-case, and in cooperation between psychiatrists, cardiologists, pharmacists, for a better control of the risk of sudden cardiac death from a psychiatric medication origin.

Evaluation of Ceftriaxone utilization in internal medicine wards of general hospitals in Addis Ababa, Ethiopia: a comparative retrospective study.

ObjectivesThe irrational use of reserved antimicrobials, such as ceftriaxone, is one of the global public health issues particularly to low income countries like Ethiopia, leading to high costs of treatment or therapeutic failure. The purpose of the present study, thus, is to evaluate the appropriateness of ceftriaxone utilization in the medicine wards of general hospitals in Addis Ababa, with reference to the standard treatment guideline of Ethiopia for general hospitals.MethodsAn institution based retrospective cross sectional study design was conducted in the internal medicine wards of Hayat and Zewditu Memorial hospital from 20 January to 20 February, 2014. Medication records of all patients who were admitted and prescribed with ceftriaxone during the previous one year to the study period were evaluated in reference to the Ethiopian Standard Treatment Guideline (STG 2010) for general hospitals.ResultsThe proportion of patients who received ceftriaxone was 59.3 % and 49 % in the public & the private hospital, respectively. Pneumonia, meningitis and sepsis were the common diagnoses in which ceftriaxone was prescribed in both hospitals. Maintenance fluids were the top ranked co-prescribed drugs in either hospital. Only 48.9 % in the public hospital and 44.6 % of records in the private hospital showed overall ceftriaxone use compliance to the guideline. Days of hospital stay was associated with appropriateness of ceftriaxone therapy.ConclusionsEven though ceftriaxone is one of the most commonly prescribed drugs in both hospitals, appropriateness of its use, according to the Ethiopian standard treatment guideline, was less than expected. This was so mainly from its indication and duration of therapy. Increasing the duration of hospital stay, however, showed to improve the appropriateness of ceftriaxone utilization.

The influence of co-prescribed GABA-ergic drugs on anti-depressant compliance in patients with depression: A prospective study in a South African private healthcare cohort

Background: Despite the progress made in recent years regarding our understanding of the neurobiology of major depressive disorder (MDD), approximately one third of patients remain unresponsive to treatment. Co-prescribing of GABA-ergic drugs (GDs), such as sedative hypnotics, with antidepressants (ADs) is not uncommon, although how they benefit the outcome, if at all, remains controversial. Adequate compliance is central to a positive outcome, although its impact with respect to drug usage patterns has not been considered. The aim of the current study is to establish how the co-prescribing of GDs is associated with altered antidepressant compliance and which antidepressants (ADs) are associated with the worst compliance in combination with GDs.

Potential drug&amp;ndash;drug interactions in HIV-infected children on antiretroviral therapy in Lagos, Nigeria

BackgroundMulti-therapy is common in HIV-infected children, and the risk for clinically significant drug interactions (CSDIs) is high. We investigated the prevalence of CSDIs between antiretroviral (ARV) and co-prescribed drugs for children attending a large HIV clinic in Lagos, Nigeria.MethodsThe case files of pediatric patients receiving treatment at the HIV clinic of the Lagos University Teaching Hospital (LUTH), Idi-Araba, between January 2005 and December 2010 were reviewed. The ARV and co-prescribed drug pairs were evaluated for potential interactions using the Liverpool HIV Pharmacology Group website. The potential interactions were rated as A (no known interaction), B (minor/no action needed), C (moderate/monitor therapy), D (major/therapy modification), and X (contraindicated/avoid combination).ResultsOf the 310 cases reviewed, 208 (67.1%) patients were at risk of CSDIs. Artemisinin-based combination therapy was prescribed for over one-half of the patients, accounting for 40% of the CSDIs. Excluding this drug class, the prevalence of CSDIs reduced from 67.1% to 18.7% in 58 patients. Most of the CSDIs (579; 97.2%) were moderately significant and frequently involved nevirapine and fluconazole (58; 9.7%), zidovudine and fluconazole (55; 9.2%), zidovudine and rifampicin (35; 5.9%), and nevirapine and prednisolone (31; 5.2%). Age (P=0.392), sex (P=0.783), and moderate (P=0.632) or severe (P=0.755) malnutrition were not associated with risk for CSDIs.ConclusionThere is a tendency for CSDIs between ARV and co-prescribed drugs among the group of children evaluated in this study. Measures are necessary to prevent important drug interactions and to manage those that are unavoidable.

Dosing of dabigatran etexilate in relation to renal function and drug interactions at a tertiary hospital

Plasma concentrations of the anticoagulant dabigatran are correlated with clinical outcomes, and are affected by renal function, intestinal P-glycoprotein (P-gp) activity and stomach acidity. To determine the adherence to dabigatran etexilate renal dosing guidelines, the frequency of co-prescription of potentially interacting drugs in patients on dabigatran, and how these related to dabigatran dosing. A retrospective chart review of 204 patients discharged from a tertiary hospital on dabigatran etexilate over a 12-month period. Creatinine clearance, using the Cockcroft-Gault equation, was used as the surrogate of renal function in the 86 patients where this was calculable. Prescribed dabigatran etexilate dose rates in relation to creatinine clearance and the manufacturer's guidelines were classified as 'standard', 'low' and 'high' in 47% (40/86), 49% (42/86) and 5% (4/86) of patients respectively. Co-prescribed drugs that potentially interact with dabigatran etexilate were present in 75% (154/204) of patients and included strong P-gp inhibitors (16%, 32/204), proton-pump inhibitors (46%, 94/204) and anti-platelet drugs (47%, 95/204). Co-prescription of strong P-gp inhibitors was associated with the prescription of 'low' dose rates relative to renal function (P = 0.025). Few patients were dosed excessively in relation to creatinine clearance. Around 50% was prescribed with 'low' dose rates in relation to creatinine clearance, which because of the association with co-prescription of strong P-gp inhibitors may be clinically appropriate. Most patients were co-prescribed with drugs that potentially interact with dabigatran etexilate.

Drug–drug interactions between antiretrovirals and drugs used in the management of neglected tropical diseases

The group of infections known as the neglected tropical diseases (NTDs) collectively affect one billion people worldwide, equivalent to one-sixth of the world's population. The NTDs cause severe physical and emotional morbidity, and have a profound effect on cycles of poverty; it is estimated that NTDs account for 534 000 deaths per year. NTDs such as soil-transmitted helminth infections and the vector-borne protozoal infections leishmaniasis and trypanosomiasis occur predominantly in the most economically disadvantaged and marginalized communities. It is estimated that all low-income countries harbour at least five of the NTDs simultaneously. NTDs are neglected because they do not individually rank highly in terms of mortality data, and because they affect populations with little political voice. There is considerable geographic overlap between areas with high prevalence of NTDs and HIV, raising the possibility of complex polypharmacy and drug-drug interactions. Antiretrovirals pose a particularly high risk for potential drug-drug interactions, which may be pharmacokinetic or pharmacodynamic in nature and can result in raising or lowering plasma or tissue concentrations of co-prescribed drugs. Elevated drug concentrations may be associated with drug toxicity and lower drug concentrations may be associated with therapeutic failure. The aim of this paper is to review the currently available data on interactions between antiretrovirals and drugs used in the management of NTDs. It is intended to serve as a resource for policy makers and clinicians caring for these patients, and to support the recent WHO 2020 Roadmap and the 2012 London Declaration on NTDs.

Clinically significant interactions between antiretroviral and co-prescribed drugs for HIV-infected children: profiling and comparison of two drug databases

BackgroundDrug–drug interactions are an important therapeutic challenge among human immunodeficiency virus-infected patients. Early recognition of drug–drug interactions is important, but conflicts do exist among drug compendia on drug interaction information. We aimed to evaluate the consistencies of two drug information resources with regards to the severity rating and categorization of the potential interactions between antiretroviral and co-prescribed drugs.MethodsWe reviewed the case files of human immunodeficiency virus-infected children who were receiving treatment at the human immunodeficiency virus (HIV) clinic of the Lagos University Teaching Hospital, Idi Araba, between January 2005 and December 2010. All of the co-prescribed and antiretroviral drug pairs were screened for potential interactions using the Medscape Drug Interaction Checker and the Monthly Index of Medical Specialties Interaction Checker. Drug–drug interaction (DDI) severity and categorization were rated on a scale of A (no known interaction); B (minor/no action needed); C (moderate/monitor therapy); D (major/therapy modification); and X (contraindicated/avoid combination).ResultsA total of 280 patients were at risk of 596 potential DDIs. The databases showed discrepancies, with Medscape database identifying 504 (84.6%) and USA MIMS database identifying 302 (50.7%) potential DDIs. Simultaneous identification of DDIs by both databases occurred for only 275 (46.1%) listed interactions. Both databases have a weak correlation on the severity rating (rs = 0.45; P < 0.001). The most common DDIs identified by the databases were nevirapine and artemisinin-based combination therapy (170; 28.5%), nevirapine and fluconazole (58; 9.7%), and zidovudine and fluconazole (55; 9.2%). There were 272 (45.6%) interaction severity agreements between the databases.ConclusionDiscrepancies occurred in DDI listings between Medscape and USA MIMS databases. Health care professionals may need to consult more than one DDI information database to ensure safe concomitant prescribing for HIV patients.

Effect of dosage failed of first antiepileptic drug on subsequent outcome

The recent definition of drug-resistant epilepsy proposed by the International League Against Epilepsy (ILAE) stipulated failure of an adequate trial of two tolerated, appropriately chosen and used antiepileptic drug (AED) schedules to achieve seizure freedom. Doses failed were not specifically discussed. We explored the effect of the doses at which the first and second AED regimens failed on subsequent outcomes in a population of adults with newly diagnosed epilepsy followed for up to 20 years. Patients in whom epilepsy was diagnosed and the first AED prescribed between July 1, 1982 and April 1, 2006, were followed until March 31, 2008. Dosage at which an AED failed was categorized according to the World Health Organization's defined daily dose (DDD) for each drug. Cumulative incidence curves for time to final seizure freedom (no seizure for at least 1 year on unchanged dosage at last follow up) were stratified by whether the first regimen was failed at doses above or below the 25%, 50%, or 75% cutoffs for the DDD of each AED. Among patients who had taken a second regimen (n = 327), those in whom the first AED failed at doses above the various cutoffs (particularly 50% and 75% DDD) had lower probability of becoming seizure-free at last follow-up (p = 0.06 for 25% DDD, p < 0.001 for both 50% and 75% DDD). The same difference was observed for patients who had taken a third regimen (n = 141; p = 0.23 for 25% DDD, p < 0.01 for 50% DDD; and p = 0.002 for 75% DDD). A trend to higher seizure-free rate was observed in patients who had taken the third regimen when both the first and second regimens failed at <75% DDD. The difference remained significant after adjusting for covariates when using 50% DDD as the cutoff for patients who took a second regimen (hazard ratio 1.60, 95% confidence interval 1.08-2.37). Higher failure dosage of the first AED predicts poorer subsequent outcome. This methodology could be used to refine further the ILAE definition of drug-resistant epilepsy by exploring the doses need to fail to provide an adequate AED trial.

Antiplatelet drugs in the elderly: prescriptions often inappropriate and reduced tolerance by associated diseases and drugs

To assess the conditions of prescriptions and tolerance of antiplatelet drugs (APD) in the elderly and to detail the parameters that influence the tolerance of these drugs. Prospective survey in a Department of Geriatric Medicine. Two hundred nineteen patients 70 years and older treated with one or two APD prior to admission were included during 7 months in 2008. We recorded the type of APD, associated diseases, main associated or co-prescribed drugs which could interact with APD and the bleeding adverse events including cutaneous bleeding. The mean age of the 219 patients was 84.5 ± 6.7 years (70-101 years), women 59.4%. Among patients 64.8% received aspirin (mainly 75 mg), 28.3% received clopidogrel and 6.8% received their combination; 16.9% of prescriptions were off-label; 51.6% of patients had an associated disease and/or an associated drug which could have increased risk of bleeding event. Among the patients who received a gastric-protective drug, the prescription followed the recommendations of the French Health Authority in 38.9%. We recorded bleeding events in 24.2% of patients at admission and in 18.3% of patients during the hospitalization. Bleeding events were significantly more frequent in patients treated with aspirin than clopidogrel (40.8 vs. 24.2%, P < 0.05) and/or with an associated drug (OR = 2.36, 95% CI 1.34-4.14, P < 0.01) and/or an associated disease (OR = 1.22, 95% CI 1.01-3.42, P < 0.05). APD treatment was stopped in 28.8% of patients, mainly because lack of indication or bleeding adverse events. Off-label prescriptions of APD were not rare in the elderly, and adverse events are frequent. The results of this preliminary study evoke that medical situations at increased risk of bleeding are perhaps insufficiently evaluated, either in case of prescription of associated drugs with increased bleeding risk or during the follow-up of patients with associated diseases. Cutaneous bleeding events should be more taken into account in prospective studies.

Integral pharmacokinetics of multiple lignan components in normal, CCl 4-induced hepatic injury and hepatoprotective agents pretreated rats and correlations with hepatic injury biomarkers

Although pharmacokinetic alternations by hepatic injury have been extensively studied, little is known about the potential influence of hepatoprotective agent's treatment. This study was aimed to investigate the holistic pharmacokinetics of multiple lignans, CYP3A regulations, and their correlations with hepatic injury biomarkers, in hepatic injured rats pretreated with or without schisandra lignan extract (SLE) and dimethyl-diphenyl-bicarboxylate (DDB). Integral pharmacokinetics of multiple lignans based on an AUC-weighting approach was determined in normal, CCl4 induced hepatic injury rats pretreated with or without SLE and DDB. Protein expression and activities of CYP3A were determined. Pharmacokinetic parameters and CYP3A activities were correlated with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. CCl4 induced acute hepatic injury resulted in a nearly 8-fold enhancement of integral plasma exposures of multiple lignans, which was caused by the significant down-regulation of CYP3A. SLE and DDB pretreatment exhibited potent hepatoprotective effects, accompanied with the restored expression and activity of CYP3A, and the recovery of the respective and integral pharmacokinetics of lignans components. The integral AUC 0–tn and CYP3A activities correlated well with ALT and AST. This study suggested that the pharmacokinetic regulating effects of hepatoprotective agent's on themselves and co-prescribed drugs should be of concern, and hepatic injury biomarkers may serve as good predictors.

Differences between SSRI's pharmacokinetics and pharmacodinamics

Selective serotonin reuptake inhibitors (SSRI) are nowadays the preferred treatment for patients with depression and anxiety disorders, when compared with traditional tricyclic antidepressants. All the SSRIs were designed to selectively potentiate serotonin [5-hydroxytryptamine (5-HT)] activity through inhibition of the 5 -HT neuronal reuptake transporter. However, despite a common mode of proven antidepressant efficacy and a similar range of indications, each SSRI has individual properties, not only pharmacodinamics, but also pharmacokinetics, which contributes for different pattern of clinical indications, side effects and interactions. The authors pretended to review the differences between each SSRI, in terms of metabolism and clinical goals. They analyzed several studies published in the last years, obtained through MedLine research. The authors describe how the unique secondary binding properties of each SSRI account for clinical significant differences in tolerability and side-effects profiles, particularly in some patients. Secondary properties within the class of SSRIs include some combinations of actions at noradrenergic, dopaminergic, muscarinic, cholinergic, histaminergic and sigma receptors. In addition, most SSRI inhibit al least one of the cytochrome P450 enzymes, resulting in potential pharmacokinetics interactions with co-prescribed drugs.

Prescription of Nonsteroidal Anti-inflammatory Drugs and Co-prescribed Drugs for Mucosal Protection: Analysis of the Present Status Based on Questionnaires Obtained from Orthopedists in Japan

Recently guidelines for the treatment and prevention of ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs) have been established. The aim of the present study was to examine factors influencing orthopedists in Japan in the use of cytoprotective drugs to prevent NSAID-associated gastrointestinal adverse events. We sent a questionnaire to 402 orthopedists in Hyogo Prefecture. A standardized 10-item questionnaire was used to collect information on NSAID prescriptions (drug name, pharmaceutical form, doses, and duration of use) and associated drugs, especially gastroprotective drugs. Two hundred eight (51.7%) orthopedists returned the questionnaire. The most frequently used NSAIDs, in descending order, were loxoprofen sodium, diclofenac sodium, and etodolac. Most doctors (80%) reported patients with abdominal symptoms associated with NSAIDs. Of these doctors, 59% treated the symptoms by themselves, and prescribed gastroprotective agents (32.2%), histamine H2-receptor antagonists (H2RAs) (26.4%), prostaglandin analogues (PAs) (17.0%), or proton pump inhibitors (PPIs) (16.2%). Sixty-seven percent of doctors reported that those drugs reduced the symptoms. Most orthopedists (96%) prescribed some type of drug to prevent NSAID-associated gastrointestinal events, including gastroprotective drugs (44.6%), H2RAs (19.5%), PAs (17.4%), and PPIs (10.8%). The doctors reported that they prescribed medicines for NSAID-associated gastrointestinal events on the basis of their experience (23%), by considering medical insurance restrictions (17%), and by referring to information provided by pharmaceutical company representatives (16%). Most orthopedists prescribe some type of drug to prevent NSAID-induced ulcers but do not refer to the guidelines. We therefore strongly recommend that the guidelines be made more widely known to gastroenterologists and to physicians in every field of clinical practice, including orthopedics.

Selectivity of SSRIs: individualising patient care through rational treatment choices

Despite a common mode of action [inhibition of the 5-hydroxytryptamine (5-HT) neuronal reuptake transporter], proven antidepressant efficacy and a similar range of indications (depression and a variety of anxiety disorders), the unique secondary binding properties of each selective serotonin reuptake inhibitor (SSRI) account for clinically significant differences in tolerability and side-effect profiles, particularly in some patients. Secondary properties within the class of SSRIs include some combination of actions at noradrenergic, dopaminergic, muscarinic cholinergic, histaminergic and sigma receptors. In addition, most SSRIs inhibit at least one of the cytochrome P450 enzymes, resulting in potential pharmacokinetic interactions with co-prescribed drugs. Although secondary properties of SSRIs can be associated with side effects, sometimes these same actions can be harnessed to good therapeutic effect through rational, informed treatment choices. In this way, agents that more consistently cause central nervous system activation (such as fluoxetine and sertraline) can be used to boost energy in patients whose depression is accompanied by fatigue and apathy, while the anxiolytic, sedative properties of others (particularly paroxetine and fluvoxamine) can be beneficial in patients with insomnia and agitation. When secondary properties are experienced as undesirable side effects, agents with greater selectivity for the serotonin transporter and without significant secondary binding properties, such as citalopram and escitalopram, may be desirable. This article explains how an understanding of the secondary binding properties of the SSRIs can guide individualised treatment across the spectrum of depressive and anxious states.

Assessment of Rational Prescribing of Antihypertensive Drug combinations in Lagos University Teaching Hospital

Purpose: The study aimed to assess prescribing trends of antihypertensives and proportion of prescriptions containing irrational combinations of antihypertensives and co-prescribed drugs. Methods: Five hundred and fifty four prescriptions, containing antihypertensives, were collected prospectively over a period of twelve months, from the internal medicine clinic of the Lagos University Teaching Hospital, and evaluated. Results: The average number of drugs prescribed per encounter was 2.9. Encounters with injections were 0.5%. The percentage of drugs prescribed by generic name was 31.6%. All the drugs prescribed were from the National Essential Drugs List. Calcium antagonists were the most frequently used group of drugs (41.3%), followed by Diuretics (33.0%) and Angiotensin-Converting Enzyme inhibitors (ACEIs) (22.4%). Nifedipine (31.9%), Methyldopa (22.4%) and Propranolol (20.2%) were the most frequently used individual drugs. Beta-blockers with Calcium antagonists (13.3%), Methyldopa with Diuretics (10.6%), Calcium antagonists with ACEIs (10.3%) were the most frequently prescribed drug combinations. Irrational drug combinations with NSAIDs were observed in 21.8% of the prescriptions. Also beta-blockers were prescribed in 22% of prescriptions for hypertensive / diabetic patients. Conclusion: There is need to educate prescribers on appropriate therapeutic combinations that would provide optimal management of hypertension and associated clinical conditions. KEY WORDS: Antithypertensive, rational, drug combination. Nig. Jnl Health & Biomed. Sciences Vol.3(1) 2004: 8-11

Recent pharmacodynamic and pharmacokinetic findings on oxaprozin

Oxaprozin has proven a safe and effective treatment for arthritic conditions. It has a low incidence of gastrointestinal side effects making it a particularly attractive therapy. Being an unselective COX-1 and COX-2 inhibitor the drug may have advantages in more effective pain relief related to both COX-1 as well as COX-2 effects. We have investigated the pharmacology of oxaprozin on (a) the biochemical components of joint destruction in vitro, and (b) the pharmacokinetic interactions of this drug with albumin in vitro in which drug interactions are modelled by competitive binding of the drug with endogenous ligands or drugs that are commonly prescribed with NSAIDs. The latter in vitro pharmacokinetic study can be considered as a basis for understanding both safety and therapeutic activity of the drug. Among the major effects of oxaprozin (10-100 μM) observed on components of joint destruction was (a) the inhibition of the production of interleukin-1β (IL-1β) from pig synovial tissues in organ culture and IL-1β, IL-6 and IL-8, as well as tumour necrosis factor-α (TNFα) from THP-1 mononuclear cells at 50-100 μM. Oxaprozin (1.0-100 μM) did not affect NO production from porcine synovial tissue, whereas indomethacin and nimesulide reduced production of NO. Oxaprozin did not exacerbate the IL-1β and/or TNFα-induced proteoglycan destruction in pig or bovine cartilage in organ culture as observed with indomethacin and aspirin. Radiolabelled oxaprozin accumulated in cartilage to a much greater extent than observed with other NSAIDs. This may be a particular advantage in enabling expression of cartilage protective effects of the drug. Albumin binding of [14C]oxaprozin (10 μM) in vitro was unaffected by other NSAIDs (e.g., aspirin, diclofenac, ibuprofen, paracetamol, salicylate), a range of commonly co-prescribed drugs (e.g., atenolol, clonidine, cromolyn, diphenhydramine, furosemide, ketotifen, salbutamol, prednisolone, theophylline), endogenous steroids (e.g., oestradiol, progesterone) or other agents (e.g., caffeine) at concentrations of 40 μM. The free concentrations of oxaprozin were, however, increased slightly by the same concentrations of warfarin, prednisolone, diazepam and captopril. In contrast, the binding of oxaprozin to free-fatty acid depleted albumin was only appreciably affected by captopril and caffeine. The free oxaprozin was slightly increased by zinc and copper ions (which are increased in rheumatic conditions) in normal as well as fatty acid-free albumin. Tryptophan release from albumin, which has a role in central analgesic actions of anti-rheumatic drugs by enhancing CNS turnover of 5-hydroxytryptamine (serotonin), was increased by 50-100 μM oxaprozin, as well as other NSAIDs. This indicates that serotonergic activation could also contributed to the analgesic properties of oxaprozin like that of other NSAIDs. These studies indicate that the potentially-significant pharmacodynamic actions of oxaprozin in arthritic joints may involve inhibition of the release of pro-inflammatory cytokines from inflamed synovium and relatively high rate of drug uptake into inflamed joints. Analgesia, in addition to being a consequence of prostaglandin inhibition, may be initiated by release of albumin-bound tryptophan and uptake into the brains leading to activate serotonergic pathways of pain suppression. Oxaprozin is only slightly affected pharmacokinetically by some co-prescribed drugs or patho-physiologic metal ions but these effects may be of limited clinical consequence principally as oxaprozin has a relatively long plasma elimination half-life (50-60 h) and any small increase in free concentrations of the drug in circulating plasma increases elimination of the drug.