The objective of this study was to determine the pharmacokinetic parameters of oclacitinib maleate as a top dress given to adult horses. Six adult horses with a mean weight of 528 kg were ...administered a single dose of 0.5 mg/kg oclacitinib maleate. Blood was collected prior to drug administration and at 15 min, 30 min, 45 min, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after treatment. Oclacitinib maleate plasma concentrations were measured by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were found best to fit a one‐compartment model. Mean Cmax was 486 ng/ml (range 423–549 ng/ml), and Tmax was estimated to be 1.7 h (range 0.3–3.1 h). The estimated T1/2 was 7.5–8 h.
In Reply Hale, Thomas W.; Baker, Teresa; Datta, Palika ...
Obstetrics and gynecology (New York. 1953),
09/2018, Letnik:
132, Številka:
3
Journal Article
To assess the direct effects of ischemia on intestinal epithelial integrity. Furthermore, clinical efforts at mitigating the effect of hypoperfusion on gut permeability have focused on restoring gut ...vascular function.
We report that, in the Caco-2 cell model of transepithelial transport, calcium glycerophosphate (CGP), an inhibitor of intestinal alkaline phosphatase F3, has a significant effect to preserve transepithelial electrical resistance (TEER) and to attenuate increases in mannitol flux rates during hypoxia or cytokine stimulation.
The effect was observable even at concentrations as low as 1 μmol/L. As celiac disease is also marked by a loss of gut epithelial integrity, the effect of CGP to attenuate the effect of the α-gliadin peptide 31-55 was also examined. In this instance, CGP exerted little effect of preservation of TEER, but significantly attenuated peptide induced increase in mannitol flux.
It appears that CGP treatment might synergize with other therapies to preserve gut epithelial integrity.
Transfer of Low Dose Aspirin Into Human Milk Datta, Palika; Rewers-Felkins, Kathleen; Kallem, Raja Reddy ...
Journal of human lactation,
05/2017, Letnik:
33, Številka:
2
Journal Article
Recenzirano
Background:
Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not ...been reported.
Research aim:
This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin.
Methods:
In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography–tandem mass spectrometry.
Results:
Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%.
Conclusion:
Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation.
Introduction:
Cyclobenzaprine is a skeletal muscle relaxant primarily used in the treatment of pain. Its use during lactation is a matter of concern as its level of exposure to infants through human ...milk is still unknown.
Main issue:
The aim of this study was to determine cyclobenzaprine concentrations in the milk samples collected from two lactating mothers.
Management:
The present study describes the analysis of cyclobenzaprine in human milk using liquid chromatography mass spectrometry, which determined the drug concentration-time profiles in human milk.
Conclusion:
This study shows low levels of concentrations of cyclobenzaprine in human milk with calculated relative infant dose of 0.5%. However, due to the sedative properties of cyclobenzaprine, regular clinical assessment of the infant is recommended to evaluate for long-term effects.
We present a case of a 27-year-old woman in whom idiopathic hypersomnolence was diagnosed in adolescence with adequate symptomatic control on daily dosage of 250 mg of modafinil. She maintained this ...dosage throughout her pregnancy and during the peripartum period, but did not breastfeed her newborn because of a lack of information on the transmission of modafinil in human breast milk. Samples of her breast milk were obtained at various times over a 24-hour period and analyzed using liquid chromatography mass spectrometry. The relative infant dose was calculated to be 5.3%, below the threshold of concern for drug passage via breast milk. This is the first reported case of modafinil transfer into human breast milk. Given the drug's use in a variety of sleep disorders, the results of this case can be used to advise breastfeeding mothers prescribed modafinil.
Morbidly placenta accreta as a cause of postpartum morbidity is increasing in incidence. One conservative option is use of methotrexate as an adjuvant therapy for the management of placenta accreta. ...There is concern that use of methotrexate in a lactating mother could potentially expose her neonate to harmful effects of this medication.
Here we report a 29-year-old woman subjected to methotrexate treatment for placenta accreta. Her child was delivered at 32 weeks weighing 3 lbs. On postpartum day 5, this patient was diagnosed with placenta accreta and treated with intramuscular methotrexate for 3 consecutive days. She received 92 mg methotrexate intramuscularly daily, and was advised not to breastfeed. She collected milk samples on day 2, the 0 hour before the second dose and at 1, 2, 4, 8, 12, and 24 hours after taking the dose. A high-performance liquid chromatography mass spectrometry method was developed to measure methotrexate and its metabolite 7-hydroxymethotrexate levels in milk samples.
Very low levels were found for both methotrexate and 7-hydroxymethotrexate in the milk samples obtained. The results indicate that methotrexate or its metabolite receded to minimum concentration over a period of 24 hours.
This case report found the relative infant dose of methotrexate to be 0.11%. Methotrexate does transfer into breast milk, although the levels detected were very low. However, caution should still be used in counseling mothers regarding breastfeeding with this toxic drug.
Oral mesalamine (5-amino salicylic acid 5-ASA) is an anti-inflammatory agent commonly used to treat inflammatory bowel disease such as ulcerative colitis and Crohn's disease. The transfer of ...mesalamine into human milk has to date been poorly described at the current dosages and newer formulations. This study was designed to determine transfer of mesalamine into human milk as a function of maternal dose and time, and dosage form.
Ten breastfeeding mothers (age 28-41 years) suffering from inflammatory bowel disease were recruited who provided milk samples at 0, 1, 2, 4, 8, 12, and 24 hours after a single daily dose of oral mesalamine in pH-dependent gastroresistant coated tablets (1.2, 2.4, 3.6, and 4.8 g). Milk samples were analyzed using liquid chromatography/tandem mass spectrometry.
A total of 10 women were enrolled for the study. The calibration curve for mesalamine was linear over a concentration range of 0.32-200 ng/mL. Irrespective of maternal dose, mesalamine levels in milk were exceedingly low. However, a wide range of mesalamine levels were observed among all the participants. The relative infant doses were all lower than 0.1% (range 0.003-0.085%).
Regardless of dose and high variability, mesalamine levels in human milk were present in exceedingly low levels. The mothers in this study reported no side effects with their infants. These results suggest that the transfer of mesalamine into milk is very low and poses minimal risks to the breastfed infant.
Abstract
Kava (Piper methysticum Forest) is a crop historically originating from west Pacific Islands. The epidemiologic studies for Pacific Island populations indicated that their cancer incidence ...rates were inversely related to the local consumptions of kava. Whereas chemopreventive efficacy of Kava ethanol extract has been shown in chemically-induced lung carcinogenesis models, its efficacy against prostate carcinogenesis is not known. In this study, we aim to evaluate the efficacy of Kava Fraction B, which is mostly kavalactones and free of flavokawains and most potent in lung carcinogenesis models, on prostatic carcinogenesis in the well-characterized C57BL/6 transgenic adenocarcinoma of mouse prostate (TRAMP) preclinical model. Previous studies by us (The Prostate, 2011) and others have suggested a paradigm of distinct lineages of carcinogenesis in this model: i.e., at least, androgen receptor (AR)-dependent glandular epithelia lesions (usually arise from the dorsal-lateral prostate DLP lobes) and AR-independent neuroendorine (NE)-like poorly differentiated (PD) carcinomas (usually derive from the ventral prostate VP lobe).
Experimentally, male C57BL/6 TRAMP mice were fed AIN93M purified diet without or with 0.4% of Kava fraction B from 8 weeks of age (WOA). Mice were euthanized at either 16 WOA or 28 WOA unless large tumors necessitated earlier sacrifice. The growth of the DLP in Kava-treated TRAMP mice were inhibited by 70% (P<0.05) from control TRAMP mice by 16 WOA. By 28 WOA, the inhibition of TRAMP DLP growth were 76% (P<0.001). Furthermore, Kava-fed TRAMP mice cohort had lower incidence of palpable and dissectable tumors (2 out of 14 mice) than control mice (7 out of 14 mice). Therefore, Kava fraction B appeared to inhibit both epithelial lineage lesions and NE-carcinogenesis. Future work will focus on 1) profiling cellular processes and molecular targets of Kava fraction B and 2) identifying active compounds in Kava Fraction B that inhibit epithelial lineage lesions and NE-carcinogenesis.
Supported in part by NCCAM AT007395 R01 and NCI CA142649 R01 grants.
Citation Format: Su-Ni Tang, Palika Datta, Peixin Jiang, Pablo Leitzman, Cheng-guo Xing, Cheng Jiang, Junxuan Lu. Suppressing effect of a Kava fraction on two lineages of prostate carcinogenesis in the transgenic adenocarcinoma of mouse prostate model. abstract. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2133. doi:10.1158/1538-7445.AM2014-2133
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