interaction study
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Author(s):  
Caitlin E. Doran ◽  
Stephanie McGrath ◽  
Lisa R. Bartner ◽  
Breonna Thomas ◽  
Alastair E. Cribb ◽  
...  

Abstract OBJECTIVE To assess drug-drug interactions between cannabidiol (CBD) and phenobarbital (PB) when simultaneously administered to healthy dogs. ANIMALS 9 healthy, purpose bred Beagles. PROCEDURES A 3-phase prospective, randomized pharmacokinetic (PK) interaction study of CBD and PB was performed as follows: phase 1, CBD PK determination and evaluation of CBD tolerability by 3 single-dose CBD (5 mg/kg, 10 mg/kg, and 20 mg/kg) protocols followed by 2-week CBD dosing; phase 2, a single-dose, 3-way, crossover PK study of CBD (10 mg/kg), PB (4 mg/kg), or CBD (10 mg/kg) administration plus PB (4 mg/kg); and phase 3, evaluation of chronic PB (4 mg/kg, q 30 d) administration followed by single-dose CBD (10 mg/kg) PK study. RESULTS Although there were variations in CBD PK variables in dogs receiving CBD alone or in conjunction with PB, significance differences in CBD PK variables were not found. No significant difference was observed in PB PK variables of dogs receiving PB alone or with CBD. During chronic CBD administration, mild gastrointestinal signs were observed in 5 dogs. At daily CBD doses of 10 to 20 mg/kg/d, hypoxia was observed in 5 dogs and increased serum alkaline phosphatase (ALP) activities (range, 301 to 978 U/L) was observed in 4 dogs. A significant increase in ALP activity was observed with chronic administration of CBD during phase 1 between day 0 and day 14. CONCLUSIONS AND CLINICAL RELEVANCE No significant PK interactions were found between CBD and PB. Dose escalation of CBD or adjustment of PB in dogs is not recommended on the basis of findings of this study.


Abstract A sensitive and accurate LC-MS/MS method was developed and validated for the simultaneous quantification of rivaroxaban (RIV) and sitagliptin (SIT) in rat plasma using apixaban as internal standard (IS). An Agilent Eclipse plus C18 column (2.1 × 100 mm, 3.5 µm, Agilent) was used for chromatographic separation with isocratic elution. Multiple reaction monitoring (MRM) using positive-ion ESI mode to monitor ion transitions of m/z 436.8→144.9 for RIV, m/z 407.7→173.8 for SIT, m/z 459.8→442.8 for IS. The procedure of method validation included selectivity, linearity, precision, accuracy, matrix effect, extraction recovery and stability were conducted according to the guidelines of EMA and FDA. The results indicated that no obvious drug-drug interactions occurred might be owing to their differences in metabolic pathways.


2021 ◽  
Author(s):  
Thangaraj Usha Bharathi ◽  
Rosalind Lallawmzuali ◽  
Subramanyamrao Prabhakarrao Kirthishree

Abstract Background: Incompatibility occurs frequently in the plant system upon intra- or interspecific crosses resulting in several pollination barriers. The modest understanding on the breeding behaviour and mechanisms governing tuberose (Polianthes tuberosa L.) through this study will direct us to appraise the pollination and post pollination events on self- and cross- incompatibility and seed set behaviour for cross breeding programme.Results: Self-pollination of tuberose cultivars Arka Prajwal, Mexican Single and Arka Sugandhi failed to produce pods upon autogamy and geitonogamy. Pollen-pistil interaction study of incompatible cultivar Arka Prajwal substantiates that pollen tube enters the ovule within 24 hours after pollination. It discharges its contents into the embryo on the 1st day after pollination and polysaccharide granules evident upon fluorescence microscopic study. The pollen tube growth rates of self and controlled pollination were similar; however, sterility was expressed in the ovary. The female gametophytic development in self and cross incompatible cultivar Arka Prajwal showed normal development initially after pollination whereas embryosac degeneration was observed at later stage. Complete degeneration of the integument and nucellar cells was also observed. Conclusions: This study is the first to elucidate the occurrence of pseudo self-incompatibility in tuberose by identifying tuberose cultivars and breeding lines which produce pods upon geitonogamy. A positive pollen-pistil interaction with the degeneration of embryosac, integument and nucellar cell and pod shrinkage, abortion and fall confirms the prevalence of the ‘Ovarian Incompatibility’ or ‘Late-Acting Incompatibility’ in tuberose.


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