Absorption of clonazepam after intranasal and buccal administration.
ABSTRACT Serum concentrations of clonazepam after intranasal, buccal and intravenous administration were compared in a cross-over study in seven healthy male volunteers. Each subject received a 1.0 mg dose of clonazepam intranasally and buccally and 0.5 mg intravenously. A Cmax of 6.3 +/- 1.0 ng ml-1 (mean; +/- s.d.) was measured 17.5 min (median) (range 15-20 min) after intranasal administration. A second peak (4.6 +/- 1.3 ng ml-1) caused by oral absorption was seen after 1.7 h (range 0.7-3.0 h). After buccal administration a Cmax of 6.0 +/- 3.0 ng ml-1 was measured after 50 min (range 30-90 min) with a second peak of 6.5 +/- 2.5 ng ml-1 after 3.0 h (range 2.0-4.0 h). Two minutes after i.v. injection of 0.5 mg clonazepam the serum concentration was 27 +/- 18 ng ml-1. It is concluded that intranasal clonazepam is an alternative to buccal administration. However, the Cmax of clonazepam after intranasal administration is not high enough to recommend the intranasal route as an alternative to intravenous injection.
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Article: Absorption of clonazepam after intranasal and buccal administration.
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ABSTRACT: Epileptic seizures are common in patients with primary or secondary malignant brain tumor. However, current knowledge on the occurrence of seizures during the end of life (EOL) phase of brain tumor patients is limited. Because symptom management with preservation of quality of life is of major importance for patients with a malignant brain tumor, particularly in the EOL, it is necessary to gain a deeper understanding of seizures and their management during this phase. We performed a systematic review of literature related to epilepsy in the EOL phase of brain tumor patients, based on the electronic resources PubMed, Embase, and Cinahl. The search yielded 442 unique records, of which 11 articles were eligible for further analysis after applying predefined inclusion criteria. Seizures occur relatively frequently in the EOL phase, particularly in patients with high-grade glioma. However, seizure management is often hampered by swallowing difficulties and impaired consciousness. Treatment decisions are largely dependent on expert opinion because a standardized approach for treating seizures in the terminal stage of brain tumor patients is still lacking.08/2014; DOI:10.1093/nop/npu018
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ABSTRACT: In order to obtain an alternative to the intravenous (i.v.) dosage form of clonazepam (CZ), an oral droplet formulation of CZ was developed previously; however, the droplet was physically unstable. Therefore, in the present study, it was attempted to develop an easily-handled dosage form, which was more physically stable and allowed rapid drug absorption from oral mucosa. A semi-solid dosage form, composed of polyethylene glycol 1500 (PEG), CZ, and oleic acid (OA) at 37/1/2 (w/w) and named PEG/CZ/OA, and a semi-solid dosage form containing PEG and CZ at 39/1 (w/w), called PEG/CZ, were prepared. Their physical stability in air at room temperature and oral mucosal absorption in rats were investigated. The semi-solid dosage forms were much more stable physically than the droplet, that is, no recrystallization of CZ was observed for at least 8 days. The effective concentration for humans and rats (20 ng/mL or more) was achieved within 30 min after buccal administration for both PEG/CZ/OA and PEG/CZ. The plasma concentration increased gradually and less varied at each time point for PEG/CZ/OA. PEG/CZ/OA was found to show more rapid and higher absorption of CZ in buccal administration than in sublingual administration. Buccal administration with the semi-solid dosage PEG/CZ with or without OA was suggested to be a possibly useful novel dosage form as an alternative to i.v. injection.Drug Development and Industrial Pharmacy 07/2011; 37(7):809-14. DOI:10.3109/03639045.2010.545069 · 2.01 Impact Factor
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ABSTRACT: Koelewijn M, Wanrooij BS. Als de patiënt niet meer kan slikken… Huisarts Wet 2006;49(10):519-24. In dit artikel bespreken we de problemen die kunnen ontstaan als een patiënt in de laatste fase van zijn leven niet meer kan slikken. Achtereenvolgens staan we stil bij vragen over uitdroging, het belang van goede mondverzorging en de mogelijkheden om noodzakelijke medicatie toe te dienen als het langs orale weg niet meer gaat. Van een aantal veelgebruikte medicijnen in deze fase komen vooral de subcutane, transdermale, rectale en transmucosale toedieningswijze aan de orde. Aan de hand van een casus laten we zien dat het de kwaliteit van leven van de patiënt kan bevorderen als de huisarts al in een eerder stadium in de palliatieve fase de medicatie herziet en alternatieve manieren van toediening overweegt. darmaandoening-farmacotherapie-mondaandoeningen-palliatieve zorg-terminale zorgHuisarts en wetenschap 10/2006; 49(10):728-735. DOI:10.1007/BF03084906