scholarly journals Stability of Methylphenidate under Various pH Conditions in the Presence or Absence of Gut Microbiota

2021 ◽  
Vol 14 (8) ◽  
pp. 733
Author(s):  
Julia Aresti-Sanz ◽  
Markus Schwalbe ◽  
Rob Rodrigues Pereira ◽  
Hjalmar Permentier ◽  
Sahar El Aidy
Keyword(s):  
Gut Microbiota ◽  
In Silico Analysis ◽  
Intestinal Bacteria ◽  
Inactive Form ◽  
High Interindividual Variability ◽  
Ritalinic Acid ◽  
Ph Conditions ◽  
Small Intestinal ◽  
The Stability ◽  
Hydrolysis Of

Methylphenidate is one of the most widely used oral treatments for attention-deficit/hyperactivity disorder (ADHD). The drug is mainly absorbed in the small intestine and has low bioavailability. Accordingly, a high interindividual variability in terms of response to the treatment is known among ADHD patients treated with methylphenidate. Nonetheless, very little is known about the factors that influence the drug’s absorption and bioavailability. Gut microbiota has been shown to reduce the bioavailability of a wide variety of orally administered drugs. Here, we tested the ability of small intestinal bacteria to metabolize methylphenidate. In silico analysis identified several small intestinal bacteria to harbor homologues of the human carboxylesterase 1 enzyme responsible for the hydrolysis of methylphenidate in the liver into the inactive form, ritalinic acid. Despite our initial results hinting towards possible bacterial hydrolysis of the drug, up to 60% of methylphenidate is spontaneously hydrolyzed in the absence of bacteria and this hydrolysis is pH-dependent. Overall, our results indicate that the stability of methylphenidate is compromised under certain pH conditions in the presence or absence of gut microbiota.

scholarly journals pH-dependent spontaneous hydrolysis rather than gut bacterial metabolism reduces levels of the ADHD treatment, Methylphenidate

2020 ◽  
Author(s):  
Julia Aresti-Sanz ◽  
Walid Maho ◽  
Rob Rodrigues Pereira ◽  
Hjalmar Permentier ◽  
Sahar El Aidy
Keyword(s):  
Intestinal Bacteria ◽  
Bacterial Metabolism ◽  
Spontaneous Hydrolysis ◽  
Adhd Treatment ◽  
High Interindividual Variability ◽  
Carboxylesterase 1 ◽  
Ph Dependent ◽  
Small Intestinal ◽  
Hydrolysis Of

AbstractMethylphenidate is absorbed in the small intestine. The drug is known to have low bioavailability and a high interindividual variability in terms of response to the treatment. Gut microbiota has been shown to reduce the bioavailability of a wide variety of orally administered drugs. Here, we tested the ability of small intestinal bacteria to metabolize methylphenidate. In silico analysis identified several small intestinal bacteria to harbor homologues of the human carboxylesterase 1 enzyme responsible for the hydrolysis of methylphenidate in the liver. Despite our initial results hinting towards possible bacterial hydrolysis of the drug, up to 60% of methylphenidate was spontaneously hydrolyzed in the absence of bacteria and this hydrolysis was pH-dependent. Overall, the study shows that pH-dependent spontaneous hydrolysis rather than gut bacterial metabolism reduces levels of methylphenidate and suggest a role of the luminal pH in the bioavailability of the drug.

SOME OBSERVATIONS ON THE PANCREATIC AMYLASE AND INTESTINAL MALTASE OF THE CHICK

1963 ◽  
Vol 41 (1) ◽  
pp. 2107-2121 ◽  
Author(s):  
B. M. Laws ◽  
J. H. Moore
Keyword(s):  
Small Intestine ◽  
Amylase Activity ◽  
Pancreatic Amylase ◽  
Ph Optimum ◽  
Modified Method ◽  
Mucosal Cells ◽  
Small Intestinal ◽  
The Stability ◽  
Hydrolysis Of

The digestive enzymes amylase and maltase were studied in acetone-dried powders or homogenates of the pancreatic and small intestinal tissues and small intestinal contents obtained from chicks of various ages. The stability of pancreatic amylase, which was relatively low in 0.15 M sodium chloride, was increased markedly by the presence of 0.02 M barbiturate buffer. The pH optimum of pancreatic amylase (chloride-activated) was 7.0 whereas that of intestinal maltase was 6.9. High levels of pancreatic amylase activity were found in the newly-hatched chick but these levels decreased during the following 20 days and then remained constant. The contrast between the high amylase and low maltase activities in the contents of the small intestine suggested that molecules of maltose, formed by the hydrolysis of starch, were absorbed as such by the mucosal cells. It appeared that maltose could be absorbed with equal facility from all sections of the small intestine of the 10-day-old chick but in the older birds maltose absorption seemed to occur more readily from the upper small intestine than from the duodenum and lower small intestine. A modified method for the determination of maltase activity is described.

SOME OBSERVATIONS ON THE PANCREATIC AMYLASE AND INTESTINAL MALTASE OF THE CHICK

1963 ◽  
Vol 41 (10) ◽  
pp. 2107-2121 ◽  
Author(s):  
B. M. Laws ◽  
J. H. Moore
Keyword(s):  
Small Intestine ◽  
Amylase Activity ◽  
Pancreatic Amylase ◽  
Ph Optimum ◽  
Modified Method ◽  
Mucosal Cells ◽  
Small Intestinal ◽  
The Stability ◽  
Hydrolysis Of

The digestive enzymes amylase and maltase were studied in acetone-dried powders or homogenates of the pancreatic and small intestinal tissues and small intestinal contents obtained from chicks of various ages. The stability of pancreatic amylase, which was relatively low in 0.15 M sodium chloride, was increased markedly by the presence of 0.02 M barbiturate buffer. The pH optimum of pancreatic amylase (chloride-activated) was 7.0 whereas that of intestinal maltase was 6.9. High levels of pancreatic amylase activity were found in the newly-hatched chick but these levels decreased during the following 20 days and then remained constant. The contrast between the high amylase and low maltase activities in the contents of the small intestine suggested that molecules of maltose, formed by the hydrolysis of starch, were absorbed as such by the mucosal cells. It appeared that maltose could be absorbed with equal facility from all sections of the small intestine of the 10-day-old chick but in the older birds maltose absorption seemed to occur more readily from the upper small intestine than from the duodenum and lower small intestine. A modified method for the determination of maltase activity is described.

scholarly journals Measurement of the Intestinal pH in Mice under Various Conditions Reveals Alkalization Induced by Antibiotics

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 180
Author(s):  
Kouki Shimizu ◽  
Issei Seiki ◽  
Yoshiyuki Goto ◽  
Takeshi Murata
Keyword(s):  
Antibiotic Treatment ◽  
High Protein Diet ◽  
Intestinal Bacteria ◽  
High Protein ◽  
Protein Diet ◽  
Germ Free ◽  
Treatment Regimens ◽  
Ph Values ◽  
Specific Pathogen ◽  
The Stability

The intestinal pH can greatly influence the stability and absorption of oral drugs. Therefore, knowledge of intestinal pH is necessary to understand the conditions for drug delivery. This has previously been measured in humans and rats. However, information on intestinal pH in mice is insufficient despite these animals being used often in preclinical testing. In this study, 72 female ICR mice housed in SPF (specific pathogen-free) conditions were separated into nine groups to determine the intestinal pH under conditions that might cause pH fluctuations, including high-protein diet, ageing, proton pump inhibitor (PPI) treatment, several antibiotic treatment regimens and germ-free mice. pH was measured in samples collected from the ileum, cecum and colon, and compared to control animals. An electrode, 3 mm in diameter, enabled accurate pH measurements with a small amount of gastrointestinal content. Consequently, the pH values in the cecum and colon were increased by high-protein diet, and the pH in the ileum was decreased by PPI. Drastic alkalization was induced by antibiotics, especially in the cecum and colon. The alkalized pH values in germ-free mice suggested that the reduction in the intestinal bacteria caused by antibiotics led to alkalization. Alkalization of the intestinal pH caused by antibiotic treatment was verified in mice. We need further investigations in clinical settings to check whether the same phenomena occur in patients.

scholarly journals Colonoscopy does not induce small intestinal bacterial overgrowth

2017 ◽  
Vol 08 (01) ◽  
pp. 12-16
Author(s):  
Ioana Gabriela Moraru ◽  
Dan Lucian Dumitraşcu
Keyword(s):  
Statistical Significance ◽  
False Negative ◽  
Bacterial Overgrowth ◽  
Intestinal Bacteria ◽  
Small Intestinal Bacterial Overgrowth ◽  
Mean Value ◽  
Intestinal Bacterial Overgrowth ◽  
Gastrointestinal Pathology ◽  
The Mean ◽  
Small Intestinal

Abstract Background and Aim: Small intestinal bacterial overgrowth (SIBO) is associated with gastrointestinal pathology and colonoscopy. This endoscopic investigation could cause changes in gut flora including the occurrence of SIBO. We looked in this study for the effect of colonoscopy (preparation and intubation) on the occurrence of SIBO. Materials and Methods: Prospective study including thirty patients with irritable bowel syndrome (IBS) diagnosed according to Rome III criteria. Two groups were designed: Twenty IBS patients that performed colonoscopy (G1) and ten IBS patients (G2) not referred to colonoscopy. All patients have been tested for the presence of SIBO using glucose hydrogen breath tests (GHBT) at the beginning of the study, on day 1. G1 patients have also been tested before colonoscopy (day 2) and 1 week after (day 9). G2 patients performed GHBT on day 1 and on day 9. Results: The peak value of expired H2 was assessed, and the mean value was calculated. There were no significant statistical differences between the mean H2 values in the 2 groups of patients on day 1. The mean level of H2 significantly decreased after preparing for colonoscopy in G1 patients (P < 0.0001). There were no significant statistical differences between the mean levels of H2 on day 2 versus day 9 in G1 patients (P = 0.176). The mean level of H2 1 week after performing colonoscopy (7.65 ppm) is higher than that obtained after preparing for it (6.3 ppm), but no statistical significance. Patients from G2 showed no statistical differences between the mean levels of H2 on day 1 versus day 9 (P = 0.6132). Patients in G1 had a significantly lower mean H2 level versus G2 patients on day 9. Conclusions: Colonoscopy does not produce SIBO. Preparing for colonoscopy influences the level of expired H2, it reduces the number of intestinal bacteria, probably trough a mechanic effect or by inflating air during the procedure. Performing GHBT too soon after colonoscopy might result in false negative results of GHBT.

Preparation and structural analysis of (±)-threo-ritalinic acid

2013 ◽  
Vol 69 (11) ◽  
pp. 1225-1228 ◽  
Author(s):  
Sara Wyss ◽  
Irmgard A. Werner ◽  
W. Bernd Schweizer ◽  
Simon M. Ametamey ◽  
Selena Milicevic Sephton
Keyword(s):  
Methyl Ester ◽  
Free Acid ◽  
Nmr Analysis ◽  
Intermolecular Hydrogen Bonds ◽  
X Ray ◽  
X Ray Crystallography ◽  
Ph Values ◽  
Ritalinic Acid ◽  
Methyl Phenidate ◽  
Hydrolysis Of

Hydrolysis of the methyl ester (±)-threo-methyl phenidate afforded the free acid in 40% yield,viz.(±)-threo-ritalinic acid, C13H17NO2. Hydrolysis and subsequent crystallization were accomplished at pH values between 5 and 7 to yield colourless prisms which were analysed by X-ray crystallography. Crystals of (±)-threo-ritalinic acid belong to theP21/nspace group and form intermolecular hydrogen bonds. An antiperiplanar disposition of the H atoms of the (HOOC—)CH—CHpygroup (py is pyridine) was found in both the solid (diffraction analysis) and solution state (NMR analysis). It was also determined that (±)-threo-ritalinic acid conforms to the minimization of negativegauche+–gauche−interactions.

Schiff base equilibria. II. Beryllium complexes of N-n-butylsalicylideneimine and the hydrolysis of the Be2+ ion

1965 ◽  
Vol 18 (5) ◽  
pp. 651 ◽  
Author(s):  
RW Green ◽  
PW Alexander
Keyword(s):  
Aqueous Solution ◽  
Schiff Base ◽  
Complex Formation ◽  
Distribution Coefficient ◽  
Dilute Aqueous Solution ◽  
The Stability ◽  
Ph Range ◽  
Hydrolysis Of ◽  
Beryllium Complexes ◽  
Equilibria In Aqueous Solution

The Schiff base, N-n-butylsalicylideneimine, extracts more than 99.8% beryllium into toluene from dilute aqueous solution. The distribution of beryllium has been studied in the pH range 5-13 and is discussed in terms of the several complex equilibria in aqueous solution. The stability constants of the complexes formed between beryllium and the Schiff base are log β1 11.1 and log β2 20.4, and the distribution coefficient of the bis complex is 550. Over most of the pH range, hydrolysis of the Be2+ ion competes with complex formation and provides a means of measuring the hydrolysis constants. They are for the reactions: Be(H2O)42+ ↔ 2H+ + Be(H2O)2(OH)2, log*β2 - 13.65; Be(H2O)42+ ↔ 3H+ + Be(H2O)(OH)3-, log*β3 -24.11.

Saliva and serum testosterone following oral testosterone undecanoate administration in normal and hypogonadal men

1983 ◽  
Vol 102 (3) ◽  
pp. 456-462 ◽  
Author(s):  
Th. Schürmeyer ◽  
E. J. Wickings ◽  
C. W. Freischem ◽  
E. Nieschlag
Keyword(s):  
Interindividual Variability ◽  
Serum Testosterone ◽  
Serum Samples ◽  
Additional Increase ◽  
Testosterone Undecanoate ◽  
Absorption Pattern ◽  
High Interindividual Variability ◽  
Normal Men ◽  
Hydrolysis Of ◽  
Testosterone Ester

Abstract. Since saliva testosterone reflects the testosterone fraction available to target tissues the therapeutic effectiveness of orally administered testosterone undecanoate was assessed by measuring testosterone in serum and saliva. Matched saliva and serum samples were obtained from 12 normal men and 8 hypogonadal men before and at hourly intervals after the oral administration of 120 mg testosterone undecanoate. The test was repeated in 3 men after they had taken 40 mg testosterone undecanoate twice daily for 4 to 5 weeks. Following testosterone undecanoate administration serum and saliva testosterone always showed parallel increases. However, the absorption curves showed a high interindividual variability in the time when maximum concentrations were reached, as well as in the maximum levels themselves. The increases in serum and saliva testosterone were similar in normal and hypogonadal men. In normal men basal levels were reached 4 h after the maximum had occurred, while in hypogonadal men testosterone levels were not different from basal levels 2 h after the maximum. The study shows that testosterone undecanoate is well absorbed from the gut and releases significantly elevated amounts of testosterone which is available to target tissues. As the absorption pattern was always parallel in both fluids, hydrolysis of the circulating testosterone ester by the tissue ifself seems to effect no additional increase of testosterone in the tissue.

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