Pharmacokinetics and dose recommendations of Niaspan® in chronic kidney disease and dialysis patients.

BACKGROUND: Niaspan® is an extended-release formulation of nicotinic acid with improved tolerability compared with the immediate-release and sustained-release formulations. It is used to treat hypertriglyceridaemia with low high-density lipoprotein levels. This type of dyslipidaemia frequently appears in patients with chronic kidney disease (CKD). Dose recommendations for these patients are not available because pharmacokinetic data are missing. The present study was performed to analyse the pharmacokinetics of prolonged-release nicotinic acid in CKD and in dialysis patients to derive dose recommendations. METHODS: Ten dialysis patients and eight patients with CKD were enrolled in a prospective, three-period, open-label pharmacokinetic study. They received in the first week 500 mg Niaspan® per day, in the second week 1000 mg/day and in the third week 1500 mg/day. On the fourth day of every treatment unit, 11 plasma samples were collected for 24 h post-dose and analysed for nicotinic acid (NA) and its metabolites nicotinamide and nicotinuric acid (NUA). RESULTS: Median plasma NA concentrations in subjects with CKD were obviously higher than in dialysis patients, but not higher than reported in patients without renal impairment. t(max) of NA were on average 0.75 h in dialysis patients and 3.0 h in CKD patients and, therefore, especially for dialysis patients, clearly shorter than expected for extended-release formulations. It is particularly noticeable that the AUC, C(max) and t(1/2) of the metabolite NUA are significantly higher in dialysis patients in comparison to CKD patients. This may indicate that the dialysis was not effective in removing this metabolite. However, there was no correlation between the incidence of flush and the concentration of NUA. Another possibility could be a drug-drug interaction with omeprazole via CYP450 enzymes. CONCLUSIONS: These data suggest that no dose adjustment of Niaspan® is necessary in patients with renal impairment. Despite an extended-release formulation of NA, we could not detect a delay in t(max) especially in dialysis patients. We found no correlation between the incidence of flush and the NUA concentration. Furthermore, there were hints of an interaction with omeprazole.

Omeprazole-induced cough in a patient with gastroesophageal reflux disease.

Persistent cough could be caused by various diseases such as postnasal drip syndrome, asthma and gastroesophageal reflux disease (GERD) or adverse event of drugs such as angiotensin-converting enzyme inhibitors. We report a case of persistent cough associated with high plasma levels of the proton pump inhibitor omeprazole in a patient with GERD. This case suggests cough as an adverse drug event to omeprazole, which is otherwise commonly prescribed for the management of GERD-related cough. Therefore, physicians should be aware of the onset or an exacerbation of cough during omeprazole therapy.

Preparation and characterization of biocompatible oil-loaded polyelectrolyte nanocapsules.

The aim of this work was to develop a novel preparation method for polyelectrolyte nanocapsules. The prepared capsules have a three-layer polyelectrolyte shell and a core consisting of medium-chain triglycerides. The preparation is based on a high-pressure homogenized emulsion that is stabilized by a modified starch, followed by the stepwise addition of the additional layer components chitosan and lambda-carrageenan. Producing polyelectrolyte nanocapsules with an average size of 130 nm without alternating with separation steps resulted in an efficient preparation technique. The characterization of the nanocapsules by zeta-potential, light-scattering techniques, nuclear magnetic resonance, and transmission electron microscopy played a major role. All ingredients are nontoxic and biocompatible. These properties could be extremely useful to the food or pharmaceutical industry for incorporating lipophilic substances. The encapsulation may be beneficial regarding improved stability and protection capability of labile substances.

Enantioselective quantification of omeprazole and its main metabolites in human serum by chiral HPLC-atmospheric pressure photoionization tandem mass spectrometry.

Omeprazole is a proton pump inhibitor drug in widespread use for the reduction of gastric acid production. It is also proposed as a test substance for the phenotyping of cytochrome CYP3A4 and CYP2C19 enzyme activities. For this purpose, it is necessary to quantify, additionally to omeprazole, the two main metabolites 5-hydroxyomeprazole and omeprazole-sulfon in human plasma. Since omeprazole is a racemic mixture of two enantiomers and its enzymatic decomposition depends in part on its chiral configuration, full information about its metabolic breakdown can only be gained by enantioselective quantification of the drug and its metabolites. We introduce a new LC-MS/MS method that is capable to simultaneously quantify omeprazole and its two main metabolites enantioselectively in human serum. The method features solid-phase extraction, normal phase chiral HPLC separation and atmospheric pressure photoionization tandem mass spectrometry. As internal standards serve stable isotope labeled omeprazole and 5-hydroxyomeprazole. The calibration functions are linear in the range of 5-750 ng/ml for the omeprazole enantiomers and omeprazole-sulfon, and 2.5-375 ng/ml for the 5-hydroxyomeprazole enantiomers, respectively. Intra- and inter-day relative standard deviations are <7% for omeprazole and 5-hydroxyomeprazole enantiomers, and <9% for omeprazole-sulfon, respectively.