Biotin uptake by human colonic epithelial NCM460 cells:  a carrier-mediated process shared with pantothenic acid

Said, Hamid M.; Ortiz, Alvaro; McCloud, Eric; Dyer, David L.; Moyer, Mary Pat; Rubin, Stanley A.

doi:10.1152/ajpcell.1998.275.5.c1365

Cited by 101 publications

(85 citation statements)

References 42 publications

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“…Biotin uptake was performed in lymphocytes from the proband and normal controls as previously reported (Said et al 1998) using Krebs-Ringer (KR) buffer (in mM: 133 NaCl, 4.93 KCl, 1.23 MgSO 4 , 0.85 CaCl 2 , 5 glucose, 5 glutamine, 10 HEPES and 10 MES, pH 7.4). Briefly, lymphocytes were harvested by centrifugation and equal amount of cells were used for uptake studies for 5 min as described previously.…”

Section: Biotin Uptake Studiesmentioning

confidence: 99%

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

et al. 2016

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Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not fulfil the stringent diagnostic criteria but have features resembling Leigh syndrome.We describe a unique presentation of Leigh-like syndrome in a 3-year-old boy with elevated 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening (NBS).Subsequent persistent plasma elevations of C5-OH and propionylcarnitine (C3) as well as fluctuating urinary markers were suggestive of multiple carboxylase deficiency (MCD). Normal enzymology and mutational analysis of genes encoding holocarboxylase synthetase (HLCS) and biotinidase (BTD) excluded MCD. Biotin uptake studies were normal excluding biotin transporter deficiency. His clinical features at 13 months of age comprised psychomotor delay, central hypotonia, myopathy, failure to thrive, hypocitrullinemia, recurrent episodes of decompensation with metabolic keto-lactic acidosis and an episode of hyperammonemia. Biotin treatment from 13 months of age was associated with increased patient activity, alertness,

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Section: Biotin Uptake Studiesmentioning

confidence: 99%

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

et al. 2016

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“…Colonic absorption of biotin has been demonstrated in humans and pigs (Sorrell et al, 1971;Barth et al, 1986). This uptake appears to be SMVTmediated, based on demonstration of an Na ϩ -dependent, specialized carrier-mediated system for biotin uptake in a human-derived, nontransformed colonic epithelial cell line (Said et al, 1998). Furthermore, our own studies have shown a significant level of mRNA encoding SMVT in fresh human colonic tissue biopsy samples, based on quantitative PCR (K. Woodford and N. Zerangue, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

XP13512 [(±)-1-([(α-Isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane Acetic Acid], A Novel Gabapentin Prodrug: I. Design, Synthesis, Enzymatic Conversion to Gabapentin, and Transport by Intestinal Solute Transporters

Cundy¹,

Branch²,

Chernov-Rogan³

et al. 2004

J Pharmacol Exp Ther

150

125

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“…The prodrug also demonstrated a 5-fold apical to basolateral preference for permeation across cultured intestinal cell monolayers. SMVT and MCT-1 are broadly expressed along the intestinal tract of rats and humans (Said et al, 1998;Juel and Halestrap, 1999;Wang et al, 1999;K. Woodford and N. Zerangue, unpublished data).…”

mentioning

confidence: 99%

XP13512 [(±)-1-([(α-Isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane Acetic Acid], A Novel Gabapentin Prodrug: II. Improved Oral Bioavailability, Dose Proportionality, and Colonic Absorption Compared with Gabapentin in Rats and Monkeys

Cundy¹,

Annamalai²,

Bu³

et al. 2004

J Pharmacol Exp Ther

120

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The absorption of gabapentin (Neurontin) is dose-dependent and variable between patients. Rapid clearance of the drug necessitates dosing three or more times per day to maintain therapeutic levels. These deficiencies appear to result from the low capacity, limited intestinal distribution, and variable expression of the solute transporter responsible for gabapentin absorption. Saturation of this transporter at doses used clinically leads to unpredictable drug exposure and potentially ineffective therapy in some patients. XP13512 [(Ϯ)-1-([(␣-isobutanoyloxyethoxy)carbonyl]aminomethyl)-1-cyclohexane acetic acid] is a novel prodrug of gabapentin designed to be absorbed by highcapacity nutrient transporters located throughout the intestine. XP13512 was efficiently absorbed and rapidly converted to gabapentin after oral dosing in rats and monkeys. Exposure to gabapentin was proportional to prodrug dose, whereas exposure to intact XP13512 was low. In rats, Ͼ95% of an oral dose of 14 C-XP13512 was excreted in urine in 24 h as gabapentin. In monkeys, oral bioavailability of gabapentin from XP13512 capsules was 84.2% compared with 25.4% after a similar oral Neurontin dose. Compared with intracolonic gabapentin, intracolonic XP13512 gave a 17-fold higher gabapentin exposure in rats and 34-fold higher in monkeys. XP13512 may therefore be incorporated into a sustained release formulation to provide extended gabapentin exposure. XP13512 demonstrated improved gabapentin bioavailability, increased dose proportionality, and enhanced colonic absorption. In clinical use, XP13512 may improve the treatment of neuropathic pain, epilepsy, and numerous other conditions by increasing efficacy, reducing interpatient variability, and decreasing frequency of dosing.Gabapentin (Fig. 1) (Kelly, 1998). Its efficacy in neuropathic pain and epilepsy may involve binding of the drug to the ␣ 2 ␦ subunit of a voltage-dependent calcium channel (Gee et al., 1996;Marais et al., 2001).The clinical pharmacokinetics of gabapentin have been studied in healthy volunteers and patients with epilepsy (McLean, 1995;Gidal et al., 1998Gidal et al., , 2000Boyd et al., 1999). Gabapentin bioavailability is dose-dependent, decreasing from an average of about 60% at a 300-mg dose to about 35% or less at doses used to treat neuropathic pain. The underlyArticle, publication date, and citation information can be found at http://jpet.aspetjournals.org. doi:10.1124/jpet.104.067959. ABBREVIATIONS: XP13512, (Ϯ)-1-([(␣-isobutanoyloxyethoxy)carbonyl]aminomethyl)-1-cyclohexane acetic acid; SMVT, sodium-dependent multivitamin transporter; MCT-1, monocarboxylate transporter type 1; HPLC, high-pressure liquid chromatography; GP, gabapentin; LC/MS/MS, liquid chromatography-tandem mass spectrometry; CSF, cerebrospinal fluid; t 1/2 , elimination half-life; T max , time to maximum concentration; AUC (0-inf) , area under the concentration versus time curve extrapolated to infinity; AUC, area under the curve.

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Biotin uptake by human colonic epithelial NCM460 cells: a carrier-mediated process shared with pantothenic acid

Cited by 101 publications

References 42 publications

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

XP13512 [(±)-1-([(α-Isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane Acetic Acid], A Novel Gabapentin Prodrug: I. Design, Synthesis, Enzymatic Conversion to Gabapentin, and Transport by Intestinal Solute Transporters

XP13512 [(±)-1-([(α-Isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane Acetic Acid], A Novel Gabapentin Prodrug: II. Improved Oral Bioavailability, Dose Proportionality, and Colonic Absorption Compared with Gabapentin in Rats and Monkeys

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