Pharmacokinetics of a single dose of oclacitinib maleate as a top dress in adult horses.

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.

Human Milk Endocannabinoid Levels as a Function of Obesity and Diurnal Rhythm.

The endocannabinoid system is involved in the regulation of a variety of physiological and cognitive processes. While the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (N-arachidonoylethanolamine, AEA) have been found in breast milk, their role(s) have yet to be determined. This study determined the normal concentration ranges of endocannabinoids (2-AG and AEA) in breast milk and the influences, if any, of obesity and diurnal rhythms on their levels. Milk samples were collected from 36 breastfeeding mothers at 4-8 weeks postpartum at each feed over a 24-h period, and further stratified into three groups based on body mass index (BMI). The samples were analyzed using liquid chromatography mass spectrometry. AEA was below the limit of detection and 2-AG levels averaged 59.3 ± 18.3 ng/mL (± SD) in women with normal BMI. Wide-ranging 2-AG concentrations in the overweight (65.5 ± 41.9 ng/mL) /obese (66.1 ± 40.6 ng/mL) groups suggest BMI may be a contributing factor influencing its levels. Following a diurnal pattern, there was a significantly higher 2-AG concentration observed during the day, as compared to night time samples. In conclusion, our study clearly suggests that appropriate milk collection and storage conditions are critical. Further, body weight and diurnal rhythm appear to influence levels of 2-AG. Based on these results, future studies are underway to determine what specific roles endocannabinoids may play in human milk and how elevated levels of 2-AG may modulate infant appetite and health.

Dexmedetomidine Levels in Breast Milk: Analysis of Breast Milk Expressed During and After Awake Craniotomy.

Background: Dexmedetomidine is an α2-adrenoreceptor agonist with utility in sedation and analgesia for the perioperative or intensive care patient. The literature regarding the safety of dexmedetomidine in lactating patients is very limited. Methods: We present a case of a lactating patient who received dexmedetomidine bolus and infusion as part of her intraoperative sedation during an awake craniotomy. Breast milk samples were expressed by the patient twice intraoperatively and twice postoperatively. All samples collected were analyzed using liquid chromatography mass spectrometry. Results: Dexmedetomidine concentrations in the breast milk were measured at various intervals and were 88 and 50 pg/mL intraoperatively, and 89 and 15 pg/mL postoperatively. Conclusion: Levels of dexmedetomidine in breast milk were exceedingly low. Interruption of breastfeeding and/or discarding expressed breast milk may not be necessary after dexmedetomidine in breastfeeding mothers. Further investigation with a larger sample size is warranted to describe safety profile of dexmedetomidine in breastfeeding infants.

Transfer of the Serotonin Modulator Vortioxetine into Human Milk: A Case Series.

Background: Vortioxetine (Trintellix) is a serotonin modulator used in the treatment of major depressive disorder in adults. There are no data presently published on the transfer of vortioxetine into human breast milk. Case Report: The present study determined the drug concentration-time profile of vortioxetine in milk samples collected from three lactating mothers, two consuming 10 mg once daily and one consuming 20 mg once daily. Milk levels were measured using liquid chromatography mass spectrometry. At a dose of 10 mg/day, the maximum concentration of vortioxetine in milk was 13.89 ng/mL. At a dose of 20 mg/day, the maximum concentration in milk was 52.32 ng/mL. The relative infant dose was calculated to be 1.1% for 10 mg dose and 1.7% for 20 mg dose. Conclusion: In these three cases, we found the levels of vortioxetine in breast milk to be low and dose proportional. However, both RID's for 10 and 20 mg doses (1.1% and 1.7%, respectively) fall below the 10% theoretical level of concern and no adverse effects were reported by the mothers. As this is a small patient sample, caution should be exercised until further studies report the safety profile of vortioxetine in breastfeeding infants.

Maternal Transfer of Cetirizine Into Human Milk.

INTRODUCTION: Cetirizine hydrochloride is a second-generation H1 histamine antagonist with Food and Drug Administration approval for treatment of allergic rhinitis and urticaria. Currently, the Food and Drug Administration does not recommend use of cetirizine during breastfeeding, as there are insufficient studies on both the transference of cetirizine into human milk and the effects of cetirizine in infants. MAIN ISSUE: To determine the concentration of cetirizine in human milk, samples were analyzed using high performance liquid chromatography mass spectrometry. MANAGEMENT: Based on calculations, relative infant dose was found to be 1.77% at 24 hr. In addition, there were no reported adverse effects seen in the infants. CONCLUSION: We suggest that transfer of cetirizine into human milk is minimal and unlikely to pose a significant risk to the breastfeeding infant. This is the first report presenting the transfer of cetirizine in human milk.

Cladribine transfer into human milk: A case report.

BACKGROUND: Cladribine is an antimetabolite used for the treatment of relapsing-remitting multiple sclerosis. At present, there are no data available on its use in breastfeeding mothers and its transfer in human milk. OBJECTIVE: We present a case of a lactating mother who donated her milk samples to study the transfer of cladribine following a 20-mg oral dose. METHODS: Analysis was done using liquid chromatography-mass spectrometry. RESULTS: The relative infant dose calculated in this study was 3.06%. CONCLUSION: This is the first case report suggesting the transfer of cladribine in human milk in measurable quantities. However, caution should be advised during lactation.

Dimethyl fumarate transfer into human milk.

Dimethyl fumarate (DMF) is approved for the treatment of relapsing-remitting multiple sclerosis. It is unknown whether DMF or its primary metabolite monomethyl fumarate (MMF) are excreted into human milk. We present two cases of lactating patients who donated milk samples to study the transfer of MMF into human milk following a week of 2 × 240 mg daily oral dose. Samples were analyzed using liquid chromatography mass spectrometry. The calculated relative infant dose was 0.019% and 0.007%. This is the first study to demonstrate that MMF is transferred into human milk, with only limited exposure to an infant.

Transfer of Dicloxacillin into Human Milk.

Background: Dicloxacillin is a beta-lactam antibiotic that is commonly used in the treatment of lactational mastitis in breastfeeding women. Although penicillins have long been considered safe for breastfeeding mothers and their infants, there is almost no data on the transfer of dicloxacillin into human breast milk despite the fact that it is commonly used for mastitis. Case Report: This study determined the drug concentration-time profile of dicloxacillin in milk samples collected from three lactating mothers consuming 500 mg dicloxacillin taken every 6 hours for treatment of mastitis. Milk levels were measured using liquid chromatography mass spectrometry. The maximum concentration of dicloxacillin in milk was 67.6 ng/mL. The relative infant dose (RID) was calculated to be 0.03%. This value is well below the theoretical level of concern of 10%. Discussion: The limited transfer of dicloxacillin into human milk is probably explained by the high plasma protein binding of dicloxacillin and its subsequent poor penetration into human milk. Conclusion: In this case series, the level of dicloxacillin in milk was found to be very low, and the RID to be only 0.03% of the maternal dose. Although the levels detected were low, dicloxacillin does transfer into breast milk. Caution should be exercised in infants with hypersensitivity to penicillins.

Rivaroxaban Treatment in Two Breastfeeding Mothers: A Case Series.

Background: Rivaroxaban (Xarelto) is a reversible direct factor Xa inhibitor used for the treatment and prevention of coagulation in numerous syndromes. There is very limited information available on the transfer of rivaroxaban into human breast milk. Case Report: This study determined the drug concentration-time profile of rivaroxaban in milk samples collected from two lactating mothers consuming 15 mg twice daily. After 21 days, each mother transitioned to 20 mg once daily. Levels in milk were measured using liquid chromatography mass spectrometry and analysis was done for both dosages. The maximum concentration of rivaroxaban observed for the 15 mg dose was 0.3 ± 0.02 µg/mL and that for the 20 mg dose was 0.26 ± 0.01 µg/mL. The relative infant dose (RID) was calculated to be 5% and 4%, respectively. Discussion: This relatively low infant dose is probably explained by the high plasma protein binding of rivaroxaban and its subsequent poor penetration into human milk. The results indicate that rivaroxaban receded to minimum concentration over a period of 12 hours. Conclusions: In these two cases, we found the levels of rivaroxaban in milk to be quite low, and the RID to be 5% of the maternal dose. Although the levels detected were low, rivaroxaban does transfer into breast milk. Caution should be exercised until further studies are conducted and report the safety profile of rivaroxaban in breastfeeding infants.

Transfer of Cyclobenzaprine into Human Milk and Subsequent Infant Exposure.

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.

Determination of Mesalamine levels in Human Milk as a Function of Dose.

BACKGROUND: 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. STUDY DESIGN: 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. RESULTS: 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%). CONCLUSION: 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.

Cyclophosphamide Use in Multiple Sclerosis: Levels Detected in Human Milk.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune inflammatory neurological disease of the central nervous system. It is the most common immune-mediated disorder, affecting >2 million people worldwide. Cyclophosphamide is an alkylating agent commonly used to treat both malignancies and immune-mediated inflammatory nonmalignant processes. At present, there are no data available on its use in breastfeeding mothers. CASE REPORT: In this study we report a 33-year-old mother who was suffering from MS. To treat her MS, stem cell transplantation protocol required preparation with multiple doses of cyclophosphamide. She had been exclusively breastfeeding for 6 months before undertaking this regimen. She voluntarily collected her milk samples at critical time points after the intravenous doses of 2.8 g cyclophosphamide for each of 4 days. Quantification of cyclophosphamide was determined using liquid chromatography coupled with tandem mass spectrometry. DISCUSSION: Low levels in milk were determined for cyclophosphamide as the area under the curve was 364.1 µg.hour/mL on day 1 and 113.9 µg.hour/mL on day 4. Maximum concentration of cyclophosphamide was observed on day 1 at 40.82 µg/mL, which peaked at 4 hours. For 24 hours, the levels gradually receded to minimum concentrations. The average relative infant dose (RID) for a period of 4 days varied from 4.7% at day 1 to 0.9% at day 4. CONCLUSIONS: Cyclophosphamide is transferred into breast milk in measurable quantities. This case report found RID of cyclophosphamide to be relatively low. However, great caution should be taken in counseling mothers regarding breastfeeding with this toxic drug.

Evaluating Transfer of Modafinil Into Human Milk During Lactation: A Case Report.

ABSTRACT: 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.

High-Dose Methotrexate Treatment in a Breastfeeding Mother with Placenta Accreta: A Case Report.

BACKGROUND: 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. CASE REPORT: 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. DISCUSSION: 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. CONCLUSION: 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.

Transfer of Inhaled Cannabis Into Human Breast Milk.

OBJECTIVE: To evaluate the transfer of delta-9-tetrahydrocannabinol and its metabolites into human breast milk after maternal inhalation of 0.1 g cannabis containing 23.18% delta-9-tetrahydrocannabinol. METHODS: In this pilot pharmacokinetic study, breast milk samples were collected from mothers who regularly consumed cannabis, were 2-5 months postpartum, and exclusively breastfeeding their infants. Women were anonymously recruited for the study. After discontinuing cannabis for at least 24 hours, they were directed to obtain a baseline breast milk sample, then smoke a preweighed, analyzed, standardized strain of cannabis from one preselected dispensary, and collect breast milk samples at specific time points: 20 minutes and 1, 2, and 4 hours. Quantification of delta-9-tetrahydrocannabinol and its metabolites in these collected breast milk samples was performed by high-performance liquid chromatography tandem mass spectrometry. RESULTS: A total of eight women were enrolled. Most were occasional cannabis smokers and one a chronic user. Delta-9-tetrahydrocannabinol was detected at low concentrations at all the time points beyond time zero. No metabolites were detected at any time point. Delta-9-tetrahydrocannabinol was transferred into mother's milk such that exclusively breastfeeding infants ingested an estimated mean of 2.5% of the maternal dose (the calculated relative infant dose=2.5%, range 0.4-8.7%). The estimated daily infant dose was 8 micrograms per kilogram per day. CONCLUSION: This study documents inhaled delta-9-tetrahydrocannabinol transfer into the mother's breast milk. Low concentrations of delta-9-tetrahydrocannabinol were detected. The long-term neurobehavioral effect of exposure to delta-9-tetrahydrocannabinol on the developing brain is unclear. Mothers should be cautious using cannabis during pregnancy and breastfeeding.

Transfer of Low Dose Aspirin Into Human Milk.

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.

Transfer of Montelukast into Human Milk During Lactation.

AIM: The aim of this study was to determine levels of montelukast in human milk and to develop a simple, sensitive analytical method using mass spectrometry. METHODS: Milk samples were collected from seven breastfeeding mothers, age 26-35 years, at 0, 1, 2, 4, 8, and 12 hours after oral ingestion of 10 mg montelukast. The samples were analyzed using a new Liquid Chromatography-Tandem Mass Spectrometry method. Area under the milk concentration time curve from zero to the time of the last sample (12 hours) was estimated by the linear trapezoidal rule. RESULTS: Average montelukast levels (Cavg) in milk were 5.3 ng/mL, and the relative infant dose was 0.68% of the maternal dose. The maximum concentration (Cmax) observed at 4 hours (Tmax) was 9.7 ng/mL. CONCLUSION: The exposure to the infant seems to be very low, far below therapeutic ranges in an infant. Our data suggest that montelukast is probably safe to use in a breastfeeding mother.