Hospital pharmacists' reinforcement of guidelines for switching from parenteral to oral antibiotics: a pilot study

Objective: The cost of antibiotics in hospitals may be reduced by streamlining, and, particularly, by early switching from the intravenous (i.v.) to the oral route of administration. The aim of the study was to evaluate the feasibility and impact of guidelines for switching, reinforced by pharmacists. Method: Patients admitted to internal medicine wards and treated with i.v. antibiotics for various infections were included for six weeks before (group A) and six weeks after (group B) the intervention. Differences in patient characteristics and their outcomes were sought between the two groups.Results: The 26 patients in group B stayed longer in hospital than the 29 in group A (13.3 vs. 9.7 days; P = 0.05). They also tended to need more time to reach the pre‐defined criteria for switching (3.6 vs. 2.4 days; P = 0.09). From that point on, they were switched more rapidly to oral antibiotics (1.5 vs. 3.2 days; P = 0.02), which resulted in a trend toward a lower treatment cost until their discharge (44 vs. 92 euros; P = 0.08). No difference was found between the 2 groups for the duration of the i.v. therapy, or the total in‐hospital cost of antibiotics. Conclusion: Pharmacists may help implement and reinforce guidelines for switching to oral antibiotics. The evaluation of such interventions implies the choice of appropriate outcomes and the awareness of confounding factors.     

Cost‐effectiveness analysis of tropisetron vs. chlorpromazine‐dexamethasone in the control of acute emesis induced by highly emetogenic chemotherapy in children

Objective. To perform a costeffectiveness analysis (CEA) between a standard antiemetic regimen chlorpromazine + dexamethasone (CPMDEX) and a 5HT3 receptor antagonist tropisetron (TROP) in the control of acute emesis induced by highly emetogenic chemotherapy in children, considering two analytic perspectives: hospital and patients. Methods. The CEA was performed by constructing a decision tree, for both analytic perspectives, of the possible outcomes of treatment with TROP (single 0.2 mg/kg i.v.) or CPM (515 mg i.v. infusion for 3 doses) plus DEX (2 mg/m2 i.v. bolus i.v. × 2). The patients were stratified by age in two groups (212 and 1317). To estimate the probability of each endpoint at the decision tree we have taken as a base a trial developed in the Department of Pediatrics. Direct medical cost of primary therapy, failure, complications and side effects were included in the cost calculations. Results. From patients' analytic perspective, TROP was more costeffective than CPMDEX for both groups of patients. Discrepancy between both analytic perspectives in 1317 yearold patient's group was resolved in favour of the option chosen from the patients' analytic perspective (TROP). Sensitivity analysis showed the reliability of the results. Conclusions. 1. TROP was more costeffective than CPMDEX. 2. Taking into account the patients' analytic perspective is essential when we compare antiemetics pharmacoeconomically. 3. It seems necessary to increase the effectiveness of TROP in pediatric patients receiving highly emetogenic chemotherapy with strategies such as the addition of a steroid.     

An observational study of intravenous medication errors in the United Kingdom and in Germany

Objectives: To investigate the incidence and the severity of intravenous (i.v.) drug preparation and administration errors in two countries and three pharmacy services. Method: A disguised observational method was used to record details of the preparation and administration of prescribed i.v. drugs on two wards in each of three teaching hospitals: one with a traditional British ward pharmacy service (TBP) and two hospitals in Germany, one with a traditional ward stock supply (TGP) and one with a satellite pharmacy service (GSP) with unit dose system. Main outcome measures: Errors in i.v. drug preparation and administration and their potential significance. Results: The number of observed preparations/administrations were: TBP 77/63, TGP 126/109 and GSP 134/106. The preparation error rates were: TBP 22% (95% confidence interval: 1331%), TGP 23% (1630%) and GSP 31% (2339%). The administration error rates were TBP 27% (1638%), TGP 49% (3958%) and GSP 22% (1430%). The percentage of administration errors on the wards with TGP was statistically significantly higher than in the other two services. Common errors at the study sites with TBP and GSP were omissions. Wrong rate of administration occurred most frequently on the wards with TGP. The majority of errors were likely to be of 'moderate' to 'severe' outcome. Careful drug chart reading could possibly reduce omission errors on the wards with TBP. A change of the German nursing law ('Krankenpflegegesetz') to legally entitle nurses to administer i.v. drugs could probably result in better training, national guidelines and standards. Conclusion: This study found a high rate of i.v. medication errors of moderate to severe significance. Changes in practice should be considered to make i.v. therapy safer for patients.     

The perceived role and skills of pharmacists in asthma management after in‐house training

Objective: To evaluate perceived roles and skills of pharmacists in asthma management before and after a training intervention that consisted of six inhouse training sessions. Method: Altogether 315 pharmacists in the intervention group and 121 pharmacists in the control group participated in the study. The data on study variables were collected by a questionnaire during the first and last training sessions.Main outcome measures: Pharmacists' perceptions of their role, perceived skills, estimates of patients receiving counselling and experienced problems.Results: Based on their ratings for 16 topics, the pharmacists' perceptions about their role in counselling asthma patients remained rather stable. Handling of the inhalers and inhalation technique were considered as the most important aspects of counselling and issues dealing with the disease were regarded as the least important. Using a selfrated scale (410 scale), pharmacists' perceived counselling skills improved in the intervention group (6.5 vs 7.6), but not in the control group (6.5 vs 6.4). In the intervention group, the pharmacists' estimates of the proportion of new users of asthma medicines receiving counselling increased from 48% to 61% and that of old users from 18% to 26%. Before the training, the most commonly experienced problem in counselling was the pharmacists' lack of knowledge and skills. After the training, pharmacists experienced problems mainly with communication. Conclusion: When pharmacists are included in the support system for any patient group, their capabilities of fulfilling their role have to be assessed. In particular, communication skills and outcomeoriented counselling require attention.     

Cost-effectiveness of periconceptional supplementation of folic acid

Background: Supplementation of folic acid prior to and in the beginning of pregnancy may prevent neural tube defects (NTDs) in newborns – such as spina bifida – and possibly other congenital malformations.Objective: To estimate cost effectiveness of periconceptional supplementation of folic acid using pharmacoeconomic model calculation.Method: Probabilities for NTDs, risk reductions through periconceptional supplementation of folic acid and lifetime costs of care for children with spina bifida were estimated using Dutch registrations and international literature.Main outcome measure: Cost effectiveness was expressed in net costs per discounted lifeyear gained. Cost effectiveness was calculated in the baseline and in sensitivity analysis.Results: Estimated cost effectiveness of periconceptional supplementation of folic acid amounts to NLG 3900(D1800) in the base case. In sensitivity analysis cost effectiveness mostly remains below NLG 10.000(D4500).Conclusion: Periconceptional supplementation of folic acid shows a favorable cost effectiveness. From pharmacoeconomic point of view this justifies further stimulation of folicacid supplementation prior to pregnancy. This can be done through targeted education by healthcare workers, such as pharmacists.     

Oral bioavailability of phenobarbital: a comparison of a solution in myvacet 9‐08, a suspension, and a tablet

Purpose: A threeway crossover study with seven healthy male volunteers was conducted to determine the relative bioavailability of phenobarbital after single dose administration of 100 mg of phenobarbital as oral solution in Myvacet 908, and as a suspension, compared with a 100 mg phenobarbital tablet. Materials and methods: At 4week intervals each subject received the solution in Myvacet 908, the suspension and the tablet in randomized order. Blood samples were collected for 48 h after each dose for analysis of phenobarbital. From the individual serum concentrationversustime curves C _maxand T _max were determined and AUC₀₄₈ was calculated. Results: All three oral dosage forms of phenobarbital are bioequivalent. No significant diffences in T _maxwere observed. Conclusion: The oral solution in Myvacet 908, and the suspension of phenobarbital proved to be bioequivalent to a tablet.     

Clinical and economic impact of a pharmacist‐intervention to promote sequential intravenous to oral clindamycin conversion

A multicentre, prospective, controlled study compared the clinical efficacy, safety and economic impact of a pharmacist intervention to promote sequential intravenous to oral clindamycin conversion. A total of 473 patients receiving intravenous clindamycin for at least 72 hours were included in the study. Two groups were established: an intervention group (204 patients) in which an informative sheet recommending the sequential treatment was provided, and a control group (269 patients). Clindamycin was prescribed for respiratory infections in 38.9% and for prophylaxis in surgery in 25.4% of the patients (71% were contaminated surgery). No difference between groups regarding sex, infection severity, health status or clinical progress was observed. Both the stepdown treatments after 72 hours of intravenous clindamycin and the change to the oral route later on, were significantly increased with the intervention (p<0.001, p<0.001 respectively). No significant differences between both groups were found in the number of patients with adverse effects associated with the IV therapy, although the incidence tended to be lower in the intervention group (49/204 intervention versus 85/269 control, p=0.07). Compliance with the recommended clindamycin dosing regimen was significantly higher in the intervention group, in which 1.3 days reduction of intravenous therapy provided an average cost savings of PTA5246 (95%CI 25567935) per treatment. A higher reduction of 1.7 days was achieved in those patients candidates for switch therapy on the third day of intravenous clindamycin. A sequential program with clindamycin may provide a costeffective alternative to conventional therapy and the introduction of an information sheet is a costeffective strategy to promote it.     

Therapy related hospital admission in patients on polypharmacy in Singapore: a pilot study

Objective: To estimate the incidence of drug-related problems (DRPs)associated hospital admission, and its correlation to polypharmacy and age.Method: A retrospective, crosssectional study in in-patients on polypharmacy in Singapore. Significant differences (p < 0.05) between number of medications taken and age of patients were tested with the chisquare test.Results: The study population consisted of 347 patients (aged 16–97) on a mean of 7.4 ± 2.1 medications. 10.8% of the study population had DRPs on admission: 71.9% of which were dominant reasons for admission, and DRPs contributed partly in the remaining cases. These DRPs were mostly avoidable, and can be broadly classified into noncompliance, adverse drug reactions, require synergistic therapy, inappropriate dose and untreated condition. 52% of these cases were made up of geriatric patients. No statistical difference was found between patients on polypharmacy and those on major polypharmacy (10 and more drugs) in having a DRP.Conclusion: In this study, DRPs contributing to hospital admission appeared to be avoidable. Geriatrics were more susceptible to DRPs and future efforts are required in managing medications prescribed for these patients to reduce such incidences.     

Inappropriate use of oral terbinafine in family practice

Objective: To review whether oral terbinafine, used for fungal nail infections, is prescribed appropriately by general practitioners Method: Crosssectional survey of forty volunteer practices. Prescribing systems were searched to identify patients who had been prescribed a course of oral terbinafine during 1998. The clinical records of five such patients in each practice were examined for additional information regarding appropriate diagnostic tests.Results: Five hundred sixtynine patients (0.25% of the population aged 12 and over) were reported to have received a course of oral terbinafine. Sixtyfour percent had been treated empirically without any recorded diagnostic test.Conclusion: Treatment of onychomycosis with terbinafine is commonly undertaken without diagnostic confirmation. This empirical treatment does not comply with locally recommended good practice.     

Relationship between pharmacokinetic parameters of gentamicin and patient characteristics and/or clinical data in patients with solid organ tumours

Gentamicin monitoring and the selection of the initial dosage are generally based on the relationship between pharmacokinetic parameters of gentamicin (GPP) and patient characteristics and/or clinical data (PC). However, the number of studies about this relationship in cancer patients is limited. Therefore, the main objective of the present study was to evaluate the relationship between GPP and PC in cancer patients and to identify different subgroups within this group of patients with unique relationship models between GPP and PC. A total of 198 cancer patients were included in the study. Firstly, GPP were estimated by the Sawchuk and Zaske regression method. Then, a linear regression analysis was performed to investigate the relationship between GPP and PC, and lastly subgroups with unique models were identified by comparing their regression models. The results revealed that the variable which was the best predictor of the distribution volume of gentamicine was the dosing weight (DW = IBW + (ABWIBW), ABW being the actual body weight and IBW the ideal body weight). Creatinine clearance (CL_CR) measured by a 24hour urine collection (CL^CRu) was the best predictor of gentamicin clearance (CL). When this value is not available, the CL^CR estimated by the formula of Crockcroft and Gault (CG), can be used. When the CG formula was used, unique models to predict CL from CL^CR were identified for patients who were obese, patients who had received highdose chemotherapy and, for subjects who had never developed aplasia following chemotherapy. Whichever the model used, the results showed that some variability in pharmacokinetic parameters of gentamicin was not explained by the models, especially in some groups of patients.     

Stabilization of oral anticoagulant therapy in hospitalized patients and characteristics associated with lack of stabilization

The initiation and stabilization of oral anticoagulant therapy in hospitalized patients in a setting without specialized medical or pharmaceutical advice, was studied. In addition, potential risk factors for lack of stabilization were studied. All patients from three wards (orthopaedic surgery, general surgery and internal medicine) in two Dutch hospitals, who were started on oral anticoagulant therapy and who gave informed consent, were included in this three months prospective followup study. When a patient had two consecutive INR's within the range 23 during hospitalization (on day 6 or later), he was defined as stable. Stable and unstable patients were compared with respect to age, gender, quetelet index, length of hospital stay, indication for oral anticoagulant therapy, induction dosing schedule of oral anticoagulant therapy, prescribing physician, type of hospital (teaching or nonteaching), concurrently used drugs, concurrently used drugs known to potentially interact with oral anticoagulant therapy (drugdrug interactions that influence INR) and (co)morbidity. A total of 125 patients, who all used acenocoumarol as oral anticoagulant, were recruited in the study. The study population mainly comprised orthopaedic discharges on prophylactic oral anticoagulants. The mean length of hospital stay was 14.5 days (median 11.0, standard deviation (SD) 10.2) for the patients included in the study (patients with a short length of stay < 6 days were excluded from the study, because of the definition of stability). 43 patients (34%) became stable during hospitalization. The second INR within the range was reached after on average 11.1 days (median 10.0, SD 4.5).18 different induction dosing schedules were used. Differences in apparent risk of INR instability were statistically associated with length of hospital stay (odds ratio (OR) 0.85, 95% confidence interal (CI) 0.780.92), concurrent use of muscoloskeletal drugs, mainly NSAIDs, (OR 1.68, 95% CI 1.042.72) and two individual prescribing physicians (OR 6.61, 95% CI 1.4729.82 for one physician and OR 0.23, 95% CI 0.060.99 for the other physician). This population has a high percentage of instability and reaches stability relatively late. The instability was associated with length of hospital stay, the concurrent use of musculoskeletal drugs (mostly NSAID's) and physician. Most of the unstable patients had INR's below therapeutic range, suggesting a conservative dosing habit. Part of the instability may also be due to the many different physicians who dose their own patients. Interventions to improve dosing may aid in better stabilization in hospitalized patients and thus in reduced length of hospital stay.     

Evaluation of vancomycin use in a large university‐affiliated hospital in eastern France in 1999

Objective: In 1999, we conducted a retrospective drug utilization review to determine the volume and pattern of vancomycin use in a universityaffiliated hospital in eastern France. Methods: Total vancomycin use was determined and expressed as vancomycin courses per 100 admitted patients and defined daily doses (DDD) of vancomycin per 100 patientdays. The indication for vancomycin use was classified as appropriate or inappropriate according to the guidelines issues by the HICPAC. Results: A total of 311 vancomycin courses were given, as 2098 DDD, giving crude incidences of 1.17 courses per 100 admitted patients and of 1.19 defined daily doses per 100 patientdays. The frequency of appropriate courses was 66.7%. Of the 63 inappropriate courses of vancomycin, 39.7% and 28.6% were empiric therapy for nosocomial and communityacquired infections, respectively, 20.6% and 6.3% were specific therapy for nosocomial and communityacquired infections, respectively, and 4.7% were prophylactic. Conclusions: This study shows that vancomycin use in our hospital resulted in a lower selection pressure than has been reported for US universityaffiliated hospitals and that comprehensive programs to improve use of vancomycin are needed in our institution.     

An accelerated stability study of 5‐flucytosine in intravenous solution

The stability of the antimycotic drug flucytosine (5FC) and the extent of 5fluorouracil (5FU) formation in 5FC intravenous solution was studied in an accelerated stability experiment. 5FC intravenous solution (10 mg/ml) was heated at 40, 60, 70, 80 and 90 C for a maximum of 131 days. At appropriate time intervals samples were taken and the concentrations of 5FC and 5FU were determined using a newly developed, stability indicating HPLCUV method. Heating the 5FC intravenous solution at 40, 60, 70, 80 and 90 C lead to 5FC decomposition of respectively 0, 8.9, 14.4, 52.5 and 61.6%. The Arrhenius plot of the 5FC decomposition is described by: Lnk5-FC decomposition = 80.1892 * 1/T 0.2396 and the 5FU formation is described by Lnk5FU formation = 13087 * 1/T + 34.4028. It is concluded that 5FC is very stable in intravenous solution at regular storing temperatures and can therefore be stored at ambient temperatures for several years before the critical limit of 95% 5FC is reached. However, the toxic and teratogen degradation product 5FU may be present in considerable amounts in the product, due to both impurities in the raw material and the formation from 5FC upon sterilisation and storage.     

Intravenous and oral antibiotics in respiratory tract infection: an international observational study of hospital practice

Background: Hospitalised patients with respiratory tract infections (RTI) frequently receive intravenous %lpar;IV) antibiotics followed by a short course of oral treatment.Objectives: To observe antibiotic use in hospitals in Germany, Spain, France, Italy and the UK and the reasons for choosing the IV route and switching to oral treatment. Methods: Research pharmacists sought the opinions of physicians and senior nurses in the completion of a semi-structured questionnaire on the treatment of RTI with IV antibiotics. Questions focussed on antimicrobials of choice, reasons for choosing IV, reasons for changing to oral administration, and duration of treatment.Results: This study recruited 796 patients with RTI, usually pneumonia. Prescribing patterns varied widely between the five hospitals. Accepted clinical criteria were only commonly cited in Germany, Spain and the UK as reasons for choosing the IV route at the beginning of the study. These were more commonly cited at the time of switch, although other criteria such as improved condition, were other significant reasons. The mean duration of IV treatment ranged from 4 days in the UK to 10 days in Italy, where most patients received the full course of treatment by the IV route. Unlike the other hospitals studied, the few patients in Italy who were switched to another form of treatment were as likely to receive intramuscular as oral administration (13% and 11%, respectively). Conclusions: The practice of and reasons for prescribing IV antibiotics varied in the hospitals studied. Objective clinical criteria were inconsistently cited as reasons for administering IV antibiotics and in general these reasons were unrelated to those given for the switch from IV to oral administration. In order for guidelines for switching from IV to oral antimicrobials to be routinely employed, explicit physiological criteria need to be recorded in a routine fashion. Closer cooperation between pharmacists and physicians may help in developing and implementing guidelines at a local level.     

Factors associated with non-response in proton pump inhibitor users: a study of lansoprazole therapy

Background: Proton pump inhibitors (PPI) demonstrate high healing rates of 8598% in clinical trials. Due to the limited knowledge regarding response and nonresponse to lansoprazole in daily practice and for the reason that resistance to PPIs is scarce, we investigated factors possibly associated with nonresponse. Methods: Data were used from a prospective, open label, observational followup study in which 10,008 lansoprazole users were followed over time. The study was designed according to the SAMM guidelines. A matched nested casecontrol design was used to compare nonresponding (cases) and responding (controls) lansoprazole users. Nonresponse was defined as worsening or nonimprovement of symptoms at the first evaluation after at least 8 weeks of use, response as disappearance or improvement of symptoms within 8 weeks of use. Controls were matched for the evaluating physician.Results: A total of 186 nonresponders and 372 responders to PPI treatment were identified as cases and controls. Age of over 60 years, heavy smoking and previous use of PPIs were significantly more common in nonresponding patients compared with responding patients. There were no differences found between the reported diagnosis regarding response. Conclusion: In daily clinical practice, previous use of PPIs, heavy smoking and an age > 60 years were significantly associated with nonresponse to treatment with lansoprazole. Previous use of PPIs in nonresponding patients might suggest resistance to PPIs. The knowledge that nonresponse drives nonresponse may encourage physicians to follow PPI users with previous PPI use more closely.     

Peri‐marketing surveillance of lamotrigine in the Netherlands: Doctors'' and patients'' viewpoints

Purpose: Evaluation of daily clinical practice in prescribing lamotrigine in refractory epilepsy patients.Methods: A collaborative, retrospective, perimarketing study was performed in in and outpatients attending one of the three Dutch epilepsy centres. Analysis of both patients' and doctors' information was performed in 520 patients using questionnaires and medical files.Results:After one year of treatment 76% of patients maintained LTG treatment, an intentiontotreat analysis showed >= 50% seizure reduction in 23% of patients; 2050% seizure reduction in 23% of patients. Six percent of patients became at least three months seizure free. In about 20% of patients seizures became less severe and shorter of duration, while in 6% an increase was found.After three months a significant decrease in number of concomitant antiepileptic drugs was found (change from mean 1,8 to 1,5 AEDs) (p=< 0.01). After twelve months the mean number of AEDs was 1,4 per patient. Overall percentage of side effects appeared to be significantly higher if patients' questionnaire data were used. Epilepsy patients considered side effects as an important factor in the choice of medication and in withdrawal of medication. Future developments of new AEDs should take this into account. Conclusion: This perimarketing study gives insight information about longterm daily use of lamotrigine, with emphasis on effectiveness. Patients complained in the questionnaires much more about sideeffects, than was known according to the medical file. Therefore, it seems necessary to perform perimarketing studies more systematically.     

Patients'' opinions of CFC‐free inhaler changeover in primary care

Objective: To determine patient's opinions regarding the changeover from CFC containing to CFCfree salbutamol. Design: Patients receiving metered dose salbutamol inhaler therapy were identified and verbal consent was obtained before a semistructured interview was performed.Setting An outpatient respiratory clinic within a busy teaching hospita. Main outcome measures: Knowledge of CFCfree inhaler therapy and acceptance of change. Results: A total of 28 patients were identified of whom only eight (29%) had been changed to a CFCfree product. Six of these (75%) had received counselling from their GP or pharmacist regarding the change. Differences were reported by all of the patients who had been changed to a CFCfree inhaler with comments including difference in taste (6 patients), difference in feel (6), less effective (1) and more effective (1). Three patients preferred the CFCfree inhaler to their previous therapy. Although 13 out of the 20 patients who had not received a CFCfree inhaler stated they were happy with the potential changeover, 10 (80%) has concerns relating to effectiveness. Conclusion: The majority of patients still receiving CFC inhalers were aware that the production of CFCcontaining products had been restricted although they were unaware of the imminent changes that would take place regarding their inhaler therapy. However, the small sample size recruited in this study may mean that the results are unrepresentative of the CFCfree implementation process in the Grampian Health Board area as a whole. Nonetheless, in view of the differences experienced by patients who received CFCfree inhalers and the concerns stated about potential lack of efficacy by patients about to be changed over, it is essential that healthcare professionals provide advice on CFCfree inhalers to all patients.     

Quantification of communication processes, is it possible?

The PAS^® system (ProblemAnalysisSolutionsystem) is developed to quantify oral communication processes during counselling in pharmacy practice. The pharmacist translates the patients' drugrelated questions into a Pcode, the analysis of the question into an Acode and finally the given solution upon the question into a Scode. The PAS^® system has been developed for two goals. First, for the registation of drugrelated questions from patients which gives the pharmacist insight in the most common issues addressed by patients. Second, it might help the pharmacist to structure the communication with the patient during the consultation. Fortyone pharmacists participated in the evaluation of the PAS^® system. The validation of the PAS^® system consisted of two phases: the external validation and the internal validation. Kappa values were calculated as a measure of agreement in the coding by the pharmacists. The kappavalue of the external validation for the P , A and Scodes for the total set of questions indicate a moderate to poor agreement. This means that pharmacists categorize drugrelated questions from patients in a different way. Therefore we conclude that the PAS system is less reliable for research purpose. The kappavalue of the internal validation for the Pcode varies from 0.42 to 0.91. For the Acode it varies from 0.07 to 0.35 and for the Scode from zero to 0.68. Internal reproducibility is good for Pcode but not for the Acode and Scode This implies that the pharmacist can use the Pcodes for registration of patients' questions in his own pharmacy. Moreover, the usage of the PAS^® system during counselling in pharmacy practice can structure the consultation.     

Determination and pharmacokinetics of dextromoramide in methadone maintenance therapy.

To study the pharmacokinetics of dextromoramide in longterm opiate addicts on methadone maintenance therapy (MMT) a reversephase HPLC technique was developed to monitor dextromoramide and methadone concentrations in plasma simultaneously. After liquidliquid extraction from plasma, dextromoramide and methadone were determined using a Supelcosil LCABZ column and a mobile phase of KH2phosphate buffer (25 mM, pH 2.5) mixed with acetonitrile (80:20, v/v) and UV detection at 206 nm. The method was found to be sufficiently sensitive, specific and reproducible to apply in six subjects on MMT for many years, receiving orally administered dextromoramide as adjuvant. Pharmacokinetic data sets for dextromoramide in each subject were conducted and analysed further, indicating short elimination halflife values (71 min, range 31152 min). Contrary to previous studies, in all subjects tested the pharmacokinetics of dextromoramide are best described using an onecompartment model.