Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intranasal lidocaine hydrochloride (LID, CAS 73-78-9) has been shown useful in the control of a series of symptoms such as migraine, cluster headache and trigeminal neuralgia in clinical studies. However, rapid nasal mucociliary clearance of intranasal solution usually affects its efficiency. In this study, a nasal gel formulation was designed using hydroxypropyl methyl cellulose (HPMC) as mucoadhesive polymer to increase the residence time of LID on the nasal mucosa. Based on the results of a preliminary single factor study, the gel formulation was optimized by central composite design to provide better drug release and bioadhesive intensity. The methods for investigating the gel's bioadhesive intensity and for spectrophotometric determination of LID were established. Then the parameters for the LID in vitro release study such as release medium, release apparatus and rotation rate were decided upon a method of f2 fit factor. The in vitro drug release property of the optimized formulation was proved to comply with the Higuchi equation.
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PMID:Hydrophilic nasal gel of lidocaine hydrochloride. 1st Communication: Preparation, formulation optimization and in vitro release study. 2006 62

Intranasal lidocaine hydrochloride (LID, CAS 73-78-9) has been widely and commonly used in the treatment of a series of symptoms such as migraine, cluster headache and trigeminal neuralgia in clinical studies. Nevertheless, rapid nasal mucociliary clearance of intranasal solution presents the predominant obstacle impacting its efficiency. In order to prolong the residence time of LID in the nasal cavity and increase its absorption, a LID nasal gel had been developed previously using hydroxypropyl methyl cellulose (HPMC) as base material. The LID nasal gel formulation has been optimized through central composite design and its in vitro release behavior has been investigated. In the present study, safety studies employing in situ toad palate model and in vivo rat nasal mucosa model showed that compared with LID nasal spray, LID nasal gel was less toxic to mucocilia. The pharmacokinetic parameters, along with olfactory and ventricle delivery of LID from nasal gel were compared with those of LID from nasal spray, intravenous injections and oral solutions in rats using microdialysis, and the drug targeting index (DTI) was used to evaluate their brain delivery. The absolute bioavailability of the optimized LID nasal gel was about 1.5 times of that of LID nasal spray which suggested a better absorption of LID from nasal gel. Moreover, the drug targeting index (DTI) of olfactory/ventricle after nasal gel and spray administration was 2.15/1.51 and 1.66/1.26, respectively. This suggested that a fraction of the LID dose could be transported directly from the nasal cavity into the central nervous system (CNS), and the brain delivery of LID can be enhanced by nasal gel.
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PMID:Hydrophilic nasal gel of lidocaine hydrochloride. 2nd communication: Improved bioavailability and brain delivery in rats with low ciliotoxicity. 2010 49

Triflusal (CAS 322-79-2) is an antiplatelet agent that irreversibly acetylates cyclooxygenase isoform 1 (COX-1) and therefore inhibits thromboxane biosynthesis. The main metabolite of triflusal, 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), possesses also antiaggregant activity. Recently a new oral 600 mg (10 ml) solution form of triflusal has been developed. The purpose of this clinical trial was to study the relative bioavailability of the new oral solution of triflusal versus the capsules formulation, both administered as a single dose. This was a randomized, two-way, cross-over, open-label, single-site phase I clinical trial, in 24 healthy volunteers who received triflusal as 600 mg oral solution and as two 300 mg capsules in a single administration separated by a washout period of at least 17 days. Blood samples were collected and plasma concentrations of HTB were measured. Pharmacokinetic parameters used for bioequivalence assessment included AUC(0-t), AUC(0-inf) and Cmax. The formulations were considered bioequivalent if the geometric mean ratios of AUC(0-t), AUC(0-inf) and Cmax were within the predetermined equivalence range (80% to 125%). Tolerability was based on the recording of adverse events (AEs), physical examination, electrocardiogram (ECG) and laboratory tests. The parameters for bioequivalence, mean [SD] values were as follows: AUC(0-t) (microg x h/ml): 3574.08 [628.17] for triflusal oral solution and 3901.78 [698.43] for triflusal capsules; AUC(0-infinity) (microg x h/ml): 4089.21 [842.54] for triflusal oral solution and 4471.33 [905.93] for triflusal capsules; Cmax, (microg/ml): 91.24 [12.88] for triflusal oral solution and 88.61 [13.46] for triflusal capsules; Cmax/AUC(0-infinity) (h(-1)): 0.03 (0.00) for triflusal oral solution and 0.02 (0.00) for triflusal capsules. The 90% confidence intervals for the ratio experimental/control by analysis of variance after log transformed AUC(0-infinity), AUC(0-t), and Cmax were within 80% to 125%. Similar results were found for the data without log transformation. All adverse events were of mild or moderate intensity and all subjects recovered. Nine and 12 subjects reported at least one adverse event during treatment with triflusal oral solution and with triflusal capsules, respectively. The most frequently reported adverse events were headache and dizziness. It was concluded that the 600-mg solution of triflusal appeared to be bioequivalent to the reference formulation capsules. Both formulations were well tolerated.
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PMID:Comparative bioavailability study of triflusal oral solution vs. triflusal capsules in healthy subjects. A single, randomized, two-way cross-over, open-label phase I study. 2018 25


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