Relative bioequivalence of amoxicillin dissolved in breast milk

BackgroundOral antibiotics use in infants in developing countries is challenging because liquid formulations are often unavailable. However, dissolving solid formulation of drugs in water poses a risk of gastrointestinal infection. Although mother's milk may be a potential vehicle, no evidence exists to indicate that antibiotics dissolved in human milk are bioequivalent to those dissolved in water. Therefore, we compared pharmacokinetic parameters of an orally administered antibiotic, amoxicillin, dissolved in human milk, to those of water-dissolved amoxicillin.MethodsA pharmacokinetic study was conducted in 16 healthy adult volunteers in a randomised crossover design. Marketed amoxicillin powder for suspension was dissolved in either human milk or water at a final concentration of 50 mg/mL, and 10 mL was given orally in a fasting state. Timed blood samples were obtained and plasma amoxicillin was quantified using liquid chromatography-mass spectrometry.FindingsResults showed that pharmacokinetic parameters, including area-under-the-curve, Cmax and half-life of the water-based and milk-based amoxicillin administration were not significantly different. 90% CIs of the ratios of these parameters in concomitant breast milk administration to those of water were within 89% and 116%, suggesting they are bioequivalent (defined as a range between 80% and 125%).InterpretationWe conclude that oral administration of amoxicillin dissolved in human milk at 50 mg/mL results in pharmacokinetics profiles comparable to amoxicillin dissolved in water. Pharmaceutical interactions between amoxicillin and breast milk are unlikely, suggesting no need to modify dosing schedules.

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Effects of Cooking Processes on Breath Hydrogen and Colonic Fermentation of Soybean

Current Nutrition & Food Science ◽

10.2174/1573401316666200226104601 ◽

2020 ◽

Vol 16 (4) ◽

pp. 488-493

Author(s):

Naoya Okumura ◽

Naoya Jinno ◽

Kentaro Taniguchi ◽

Kenichi Tanabe ◽

Sadako Nakamura ◽

...

Keyword(s):

Healthy Adult ◽

Area Under The Curve ◽

Cooking Methods ◽

Breath Hydrogen ◽

Gas Chromatograph ◽

Colonic Fermentation ◽

Hydrogen Molecules ◽

Nutritional Analysis ◽

Hydrogen Level ◽

Adult Volunteers

Background: Soybean is rich in dietary fibers; consequently, soybean ingestion considerably increases the breath level of hydrogen molecules via anaerobic colonic fermentation. However, the influence of cooking methods on this effect, which can affect the overall health benefits of soybean, remains unknown. Objectives: The aim is to examine whether different methods of cooking soybean affect the colonic fermentation process. Methods: Nine healthy adult volunteers participated in the study; they ingested either roasted soybean flour (kinako) or well-boiled soybean (BS). Differences in their breath components were compared. Both test meals were cooked using 80 g of soybeans per individual. After a 12 h fast, the participants ate the test meals, and their breath hydrogen level was analyzed every 1 h for 9 h by using a gas chromatograph with a semiconductor detector. In addition, particle size distribution and soluble/ insoluble fibers in the feces were examined. Results: The oro-cecal transit time did not significantly differ between individuals who ingested kinako and BS. However, the area under the curve between 7 and 9 h after the ingestion of BS was significantly increased compared with that after the ingestion of kinako. The nutritional analysis indicated that the content of both soluble and insoluble fibers in BS was higher than that in kinako. In addition, the levels of unfermented fragments and soluble/insoluble fibers in the feces were increased after the ingestion of kinako compared with those after the ingestion of kinako. Conclusion: Cooking methods alter the composition of non-digestible fibers in soybean, and this can result in the lack of fermentative particles in the feces, thereby causing alterations in the breath level of hydrogen via colonic fermentation.

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Gastroduodenal Motility in Neonates: Response to Human Milk Compared With Cow's Milk Formula

PEDIATRICS ◽

10.1542/peds.80.3.434 ◽

1987 ◽

Vol 80 (3) ◽

pp. 434-438

Author(s):

T. Tomomasa ◽

P. E. Hyman ◽

K. Itoh ◽

J. Y. Hsu ◽

T. Koizumi ◽

...

Keyword(s):

Breast Milk ◽

Human Milk ◽

Infant Formula ◽

High Amplitude ◽

Cow’S Milk ◽

Milk Formula ◽

Wave Form ◽

Fasting State ◽

Cow's Milk ◽

Gastroduodenal Motility

It is known that breast milk empties more quickly from the stomach than does infant formula. We studied the difference in gastroduodenal motility between neonates fed with human milk and those fed with infant formula. Twenty-four five-to 36-day-old neonates were fed with mother's breast milk or with a cow's milk-based formula. Postprandlial gastroduodenal contractions were recorded manometrically for three hours. Repetitive, high-amplitude nonmigrating contractions were the dominant wave form during the postprandial period. The number of episodes, duration, amplitude, and frequency of nonmigrating contractions were not different following the different feedings. The migrating myoelectric complex, which signals a return to the interdigestive (fasting) state, appeared in 75% of breast milk-fed infants but only 17% of formula-fed infants (P < .05) within the three-hour recording period. Because contractions were similar following the two meals, but a fasting state recurred more rapidly in breast-fed infants, we conclude that factors other than phasic, nonpropagated antroduodenal contractions were responsible for the differences in gastric emptying between breast milk and formula.

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The Association between Maternal Stress and Glucocorticoid Rhythmicity in Human Milk

Nutrients ◽

10.3390/nu13051608 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1608

Author(s):

Michelle Romijn ◽

Luca J. L. van Tilburg ◽

Jonneke J. Hollanders ◽

Bibian van der Voorn ◽

Paul de Goede ◽

...

Keyword(s):

Psychological Distress ◽

Breast Milk ◽

Human Milk ◽

Area Under The Curve ◽

Control Group ◽

Increased Risk ◽

Liquid Chromatography Tandem Mass ◽

Highly Correlated ◽

The Impact ◽

Diurnal Rhythmicity

Background: Chronic stress is often accompanied by alterations in the diurnal rhythm of hypothalamus–pituitary–adrenal activity. However, there are limited data on the diurnal rhythmicity of breast milk glucocorticoids (GCs) among women with psychological distress. We compared mothers who sought consultation at an expertise center for pregnant women with an increased risk of psychological distress with control mothers for GC diurnal rhythmicity in milk and saliva obtained at the same time. Methods: We included 19 mothers who sought consultation at the psychiatry–obstetric–pediatric (POP) outpatient clinic and 44 control mothers. One month postpartum, mothers collected on average eight paired milk and saliva samples during a 24 h period. GC levels were measured using liquid chromatography–tandem mass spectrometry. GC rhythmicity parameters were determined with specialized software. Results: For both milk and saliva, no group differences regarding GC rhythms were found. Milk cortisol area under the curve with respect to the ground was lower in the POP group than in the control group (p = 0.02). GC levels in human milk and saliva were highly correlated within each group (p < 0.001). Conclusion: Although there were no differences between groups in GC rhythmicity, the total amount of milk cortisol was lower in the POP group. Long-term follow-up is needed to address the impact of vertical transmission of breast milk GCs.

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Pharmacokinetic and Pharmacodynamic Comparison of Chinese Herbal Ointment Liu-He-Dan and Micron Liu-He-Dan Ointment in Rats with Acute Pancreatitis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/389576 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Shi-Feng Zhu ◽

Wei-Wei Chen ◽

Jin Xiang ◽

Xian-Lin Zhao ◽

Mei-Hua Wan ◽

...

Keyword(s):

Mass Spectrometry ◽

Acute Pancreatitis ◽

High Performance ◽

Area Under The Curve ◽

Pharmacokinetic Parameters ◽

Liquid Chromatography Mass Spectrometry ◽

Pharmacokinetics And Pharmacodynamics ◽

Chinese Herbal ◽

Aloe Emodin ◽

Mass Spectrometry Mass Spectrometry

Aim. To compare the pharmacokinetics and pharmacodynamics of herbal ointment Liu-He-Dan (LHD) and micron LHD (MLHD) in rats with acute pancreatitis (AP).Methods. Twenty rats were allocated into normal, AP, LHD, and MLHD groups. LHD or MLHD was applied on rats’ abdomens. Plasma levels of emodin, rhein, aloe emodin, physcion, and chrysophanol were determined by high performance liquid chromatography—mass spectrometry—mass spectrometry (HPLC-MS-MS) at different time points, and the pharmacokinetic parameters were calculated. Serum amylase, TNF-α, IL-6, and IL-10 levels, and the pancreatic pathological scores were determined at 48 h after LHD or MLHD treatment.Results.T1/2αand area under the curve (AUC) of emodin in the MLHD group were lower than those in the LHD group, whileT1/2αand AUC of aloe emodin in the MLHD group were higher than those in the LHD group(P<0.05).T1/2αandTmaxof physcion in the MLHD group were significantly shorter than those in the LHD group(P<0.05). Compared with the AP group, the amylase, malondialdehyde (MDA), TNF-α, and IL-6 levels decreased significantly after three days of treatment in LHD and MLHD groups, while the levels of superoxide dismutase (SOD), TNF-α, and the pancreatic pathological score, were similar. The pharmacodynamic parameters between the LHD and MLHD groups were similar.Conclusion. MLHD had better pharmacokinetics than, and similar pharmacodynamics to, LHD in the management of rats with AP, which indicated that MLHD might be substituted for LHD in the treatment of AP and thus reduce the amount of medicinal herbs used.

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Bioavailability of sorafenib tablets administered as a liquid suspension

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e14549 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e14549-e14549

Author(s):

J. T. Lettieri ◽

R. Dubowy ◽

C. Xia ◽

C. Rotolo ◽

M. A. Zinny

Keyword(s):

Geometric Mean ◽

Plasma Concentrations ◽

Area Under The Curve ◽

Pharmacokinetic Parameters ◽

Liquid Chromatography Mass Spectrometry ◽

Healthy Male ◽

Noncompartmental Analysis ◽

Spectrometry Method ◽

Multikinase Inhibitor ◽

Liquid Suspension

e14549 Background: Sorafenib is a multikinase inhibitor currently approved by the FDA for the treatment of advanced renal-cell carcinoma (RCC) and unresectable hepatocellular carcinoma (HCC), and by the EMEA for the treatment of HCC and advanced RCC. Sorafenib is available as a tablet formulation. Some patients who are unable to swallow tablets have suspended sorafenib tablets in a liquid for ease of administration. We performed a study to assess whether this process alters the bioavailability of sorafenib. Methods: Twenty-six healthy male volunteers were enrolled. Utilizing a randomized, crossover design, subjects received either two 200-mg intact tablets (IT) with 8 ounces water, or two 200-mg tablets disintegrated over 10 minutes in 2 ounces of water (ST), with an additional 6 ounces of water swallowed as a rinse of the dosing vessel. Doses were separated by a 10- to 14-day washout period. Following each dose, blood samples were collected at designated times up to 144 hours after dosing for measurement of sorafenib plasma concentrations. Sorafenib was assayed by a validated liquid chromatography/mass spectrometry method. The pharmacokinetic parameters area under the curve (AUC), maximum concentration (Cmax) and time to Cmax (Tmax) were assessed by noncompartmental analysis. Results: Geometric mean (percentage coefficient of variation) or median results for these pharmacokinetic assessments are shown in the table. Conclusions: The pharmacokinetics of sorafenib, when administered as a liquid suspension of tablets in water, were similar to the pharmacokinetics of tablets swallowed whole. [Table: see text] [Table: see text]

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A Single-Dose, Two-Way Crossover, Open-Label Bioequivalence Study of an Amphetamine Extended-Release Oral Suspension in Healthy Adults

Journal of Attention Disorders ◽

10.1177/1087054717743329 ◽

2017 ◽

Vol 24 (3) ◽

pp. 414-419 ◽

Cited By ~ 1

Author(s):

Carolyn Sikes ◽

Jeffrey G. Stark ◽

Russ McMahen ◽

Dorothy Engelking

Keyword(s):

Single Dose ◽

Extended Release ◽

Healthy Adult ◽

Bioequivalence Study ◽

Oral Suspension ◽

Pharmacokinetic Parameters ◽

Open Label ◽

Adult Participants ◽

Study Results ◽

Adult Volunteers

Objective: The purpose of this study was to compare the pharmacokinetics of a new extended-release amphetamine oral suspension (AMP XR-OS) with a standard extended-release mixed amphetamine salts product, Adderall XR®. Method: In this single-dose, open-label, randomized, two-period, two-treatment crossover study, 42 healthy adult volunteers received 15 mL of AMP XR-OS in one period and a 30 mg Adderall XR capsule in another period (both containing 18.8 mg of amphetamine base) under fasted conditions. Blood samples were analyzed for d- and l-amphetamine concentrations, and pharmacokinetic parameters Cmax, AUC0-5, AUC5-last, and AUCinf were calculated to determine bioequivalence. Safety was monitored throughout the study. Results: The 90% confidence intervals (CIs) for the log-transformed Cmax, AUC0-5, AUC5-last, and AUCinf fell within the accepted 80% to 125% range for establishing bioequivalence for d- and l-amphetamine. The most common adverse events were nausea and decreased appetite. Conclusion: AMP XR-OS is bioequivalent to Adderall XR in healthy adult participants.

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Open-Label Crossover Oral Bioequivalence Pharmacokinetics Comparison for a 3-Day Loading Dose Regimen and 15-Day Steady-State Administration of SUBA-Itraconazole and Conventional Itraconazole Capsules in Healthy Adults

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00400-20 ◽

2020 ◽

Vol 64 (8) ◽

Cited By ~ 1

Author(s):

George R. Thompson ◽

Phoebe Lewis ◽

Stuart Mudge ◽

Thomas F. Patterson ◽

Bruce P. Burnett

Keyword(s):

Steady State ◽

Healthy Adult ◽

Area Under The Curve ◽

Drug Level ◽

Loading Dose ◽

Open Label ◽

Subsequent Dose ◽

State Administration ◽

Dose Study ◽

Adult Volunteers

ABSTRACT Super bioavailability (SUBA) itraconazole (S-ITZ), which releases drug in the duodenum, and conventional itraconazole (C-ITZ), which releases drug in the stomach, were compared in two pharmacokinetic (PK) studies: a 3-day loading dose study and a 15-day steady-state administration study. These were crossover oral bioequivalence studies performed under fed conditions in healthy adult volunteers. In the loading dose study, C-ITZ (two doses of 100 mg each) and S-ITZ (two doses of 65 mg each) were administered three times daily for 3 days and once on day 4 (n = 15). For the steady-state administration study, C-ITZ (two doses of 100 mg each) and S-ITZ (two doses of 65 mg each) were administered twice daily for 14 days and a last dose was administered 30 min after a meal on day 15 (n = 16). Blood samples collected throughout both studies were analyzed for ITZ and hydroxy-ITZ (OH-ITZ) levels. Least-squares geometric means were used to compare the maximum peak concentration of drug after administration at steady state prior to administration of the subsequent dose (Cmax_ss), the minimum drug level after administration prior to the subsequent dose (Ctrough), and the area under the curve over the dosing interval (AUCtau) of each formulation. The ratios of itraconazole (ITZ) and OH-ITZ for S-ITZ to C-ITZ were between 107% and 118% in both studies for Cmax_ss, Ctrough, and AUCtau, which were within the U.S. FDA-required bioequivalence range of 80% to 125%. At the end of the steady-state administration study, 13 of 16 volunteers obtained higher mean ITZ blood Ctrough levels of >1,000 ng/ml when they were administered S-ITZ (81%) than when they were administered C-ITZ (44%). The study drugs were well tolerated in both studies, with similar adverse events (AEs). All treatment-emergent AEs resolved after study completion. One volunteer receiving C-ITZ discontinued due to a treatment-unrelated AE in the steady-state administration study. No serious AEs were reported. Total, trough, and peak ITZ and OH-ITZ exposures were similar between the two formulations. Therefore, SUBA-ITZ, which has 35% less drug than C-ITZ, was bioequivalent to C-ITZ in healthy adult volunteers and exhibited a safety profile similar to that of C-ITZ.

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Pharmacokinetics of Orally Administered Prednisolone in Alpacas

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.745890 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ricardo Videla ◽

Carla Sommardahl ◽

Joe Smith ◽

Deanna M. W. Schaefer ◽

Sherry Cox

Keyword(s):

Oral Administration ◽

Half Life ◽

Maximum Concentration ◽

Healthy Adult ◽

Area Under The Curve ◽

Pharmacokinetic Parameters ◽

Elimination Half Life ◽

Cell Counts ◽

Elimination Half ◽

Intravenous And Oral Administration

This study aimed to determine the pharmacokinetics of prednisolone following intravenous and oral administration in healthy adult alpacas. Healthy adult alpacas were given prednisolone (IV, n = 4), as well as orally (PO, n = 6). Prednisolone was administered IV once (1 mg/kg). Oral administration was once daily for 5 days (2 mg/kg). Each treatment was separated by a minimum 4 month washout period. Samples were collected at 0 (pre-administration), 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, and 24 h after IV administration, and at 0 (pre-administration), 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, 24 after the first and 5th PO administration. Samples were also taken for serial complete blood count and biochemistry analysis. Prednisolone concentration was determined by high pressure liquid chromatography. Non-compartmental pharmacokinetic parameters were then determined. After IV administration clearance was 347 mL/kg/hr, elimination half-life was 2.98 h, and area under the curve was 2,940 h*ng/mL. After initial and fifth oral administration elimination half-life was 5.27 and 5.39 h; maximum concentration was 74 and 68 ng/mL; time to maximum concentration was 2.67 and 2.33 h; and area under the curve was 713 and 660 hr*ng/mL. Oral bioavailability was determined to be 13.7%. Packed cell volume, hemoglobin, and red blood cell counts were significantly decreased 5 days after the first PO administration, and serum glucose was significantly elevated 5 days after the first PO administration. In conclusion, serum concentrations of prednisolone after IV and PO administration appear to be similar to other veterinary species. Future research will be needed to determine the pharmacodynamics of prednisolone in alpacas.

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