Indexed plasma drug concentrations for drug adherence screening in hypertensive patients.

AIM: Due to its high sensitivity, qualitative plasma drug screening by liquid chromatography/tandem mass spectrometry may not be able to distinguish same-day drug intake from drug use on preceding days and cause misclassifications of drug adherence in hypertensive patients. Analysis of plasma drug concentrations may provide more accurate results. PATIENTS AND METHODS: We describe dose-dependent indexing of plasma drug concentrations for expected peak concentrations to define individual screening thresholds for same-day drug use. To explore its utility, plasma samples from 9 hypertensive patients without major comorbidity were prospectively analyzed on two occasions. All were on hydrochlorothiazide with either amlodipine (n=7) and/or valsartan (n=6) at different doses. Drugs were quantitated by mass spectrometry. Non-adherence was defined if an indexed drug concentration was below the expected trough level at 24-hour dosing interval. RESULTS: All patients were adherent by qualitative plasma screening (spectrometric sensitivity). On the first visit (random sampling time), mean plasma concentrations of the drugs were 102±70, 15.4±6.7 and 2529±1608ng/mL, and mean indexes 84±57%, 85±35% and 60±38%, respectively. Using the study criterion, non-adherence was suspected in three. Intraindividual cross-checking retained two. On the second visit (fixed sampling time), amlodipine concentration was 15.6±8.5ng/mL (88±52% after indexing). Two patients were non-adherent according to the study criterion. CONCLUSION: Indexing of plasma drug concentrations appears practicable and useful for drug adherence screening under clinical conditions. With this technique, same-day drug intake can be easily distinguished which reduces the risk of false positive results associated with qualitative drug screening.

[Drug-induced toxic hepatitis]. / Medikamentös-toxische Hepatitis.

A 55-year-old male patient was hospitalized with severe nausea, vomiting and icterus. Laboratory testing showed hepatocellular damage. After exhaustive testing, the exclusion diagnosis of a toxic hepatitis was reached. There was a strong temporal correlation with the ingestion of Hong Hua 29, a preparation from Traditional Chinese Medicine (TCM). This medication had been started twelve days prior to the first appearance of symptoms. The existing drug regimen included gabapentin (Neurontin), esomeprazole (Nexium) and prednisone (Prednison Streuli) for the therapy of an acute sensory and motor neuropathy of unknown aetiology. After cessation of Hong Hua 29, gabapentin and esomeprazole, transaminase levels started to declined and normalized within three months. According to the Swissmedic criteria of imputability, a causal correlation between the observed symptoms and the administration of Hong Hua 29 is possible.

[Unexpected loss of therapeutic effect of oxcarbazepine]. / Ungewöhlicher Wirkungsverlust von Oxcarbazepin.

After months of successful analgesic therapy with oxcarbazepine, a 52-year old woman with trigeminal neuralgia suddenly experienced episodes of heavy trigeminal attacks regularly in the evening at about the same time. Asked about changes in daily life or eating habits, she reported the ingestion of healing earth daily in the morning. After stopping the ingestion of healing earth, analgesic control of trigeminal neuralgia was restored without any changes of the initial pharmacotherapy. In daily practice, interactions which significantly influence the absorption of drugs are often overlooked. The documentation of these interactions in drug interaction databases, in the prescribing information, and in the literature is sparse though clinically relevant. Separating the ingestion of interacting substances by a time interval may not sufficiently avoid the interaction in every case. Particular caution is warranted when slow-release cation containing drugs or substances with entero-hepatic circulation are used.