Bioavailability of Citrate from Two Different Preparations of Potassium Citrate

Harvey, Jack; Zobitz, Margaret M.; Pak, Charles Y.C.

doi:10.1002/j.1552-4604.1989.tb03338.x

Cited by 13 publications

(7 citation statements)

References 5 publications

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“…This speculation, however, needs further investigation. Harvey et al [38] demonstrated that potassium citrate load caused a significant increase in urinary potassium up to 6 h, and also caused significant increase in urine pH. As a significant difference of increase in urine pH between LPR and water loads was not observed, an increase in urine pH after LPR and water loads that was found in this study may be due to the provided meals rather than water or LPR.…”

Section: Discussioncontrasting

confidence: 62%

“…Concentration of urinary citrate was maximized at 2 h after citric acid load [37]. We found the peak of urinary citrate concentration at 1 h after LPR load, and it persistently elevated for 2 h. Harvey et al [38] investigated the bioavailability of citrate from potassium citrate drugs in 18 normal volunteers and found that urinary citrate excretion was significantly increased at 1 h after dosing (60 mEq) and remained significantly high for 4-5 h. Although it cannot be directly compared, it is a clue that our LPR has a slightly lower bioavailability of citrate relative to the potassium citrate preparation. The actual reason remains to be elucidated.…”

Section: Discussionmentioning

confidence: 69%

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In vitro anti-lithogenic activity of lime powder regimen (LPR) and the effect of LPR on urinary risk factors for kidney stone formation in healthy volunteers

et al. 2015

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Hypocitraturia, hypokaliuria, and increased oxidative stress are common lithogenic risk factors found in nephrolithiasis patients, especially in Thailand. We previously developed lime powder regimen (LPR), and demonstrated that LPR delivered citraturic, alkalinizing, and antioxidative effects in kidney stone patients. In this study, in vitro anti-lithogenic activity, in vivo acute toxicity, and crossover-designed phase 1 trial (in 13 healthy volunteers) of LPR were investigated. LPR inhibited the growth of calcium oxalate monohydrate (COM) crystals in dose-dependent manner, and inhibited the intracellular production of reactive oxygen species (ROS) in COM-treated HK-2 cells. LPR did not significantly alter viability of HK-2 cells. No acute toxicity was detected in mice orally fed with LPR (10 g/kg). No adverse effect and complaint of LPR ingestion (5 g/dose) were observed in the tested volunteers. Plasma citrate was elevated at 30 min after LPR load, which was higher than the water load control. Plasma potassium was significantly elevated at 30 min after LPR load and remained high for 2 h, and at 2 h, it was significantly higher than the water load. Urinary citrate was significantly increased at 1 h after LPR load and remained high for 2 h, and at 2 h, it was significantly higher than the water load. Urinary potassium was significantly increased at 1 h after LPR load and remained high for 3 h, and its levels at 1, 2, and 3 h were significantly higher than the water load. Urinary total antioxidant status was significantly increased at 2 h after LPR load. In conclusion, LPR had an inhibitory effect on COM growth and exerted as antioxidant to attenuate ROS production in the COM-treated renal tubular cells. LPR provided citraturic, kaliuric, and antioxidative responses in healthy individuals without any adverse events. This suggests that LPR is well tolerated and safe for daily consumption.

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Section: Discussioncontrasting

confidence: 62%

Section: Discussionmentioning

confidence: 69%

In vitro anti-lithogenic activity of lime powder regimen (LPR) and the effect of LPR on urinary risk factors for kidney stone formation in healthy volunteers

et al. 2015

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“…Whereas urine of the Ank ank/ank mice still contained substantial amounts of citrate, that of the human patient lacking functional ANKH was virtually devoid of citrate. This difference might be partly explained by dietary differences: Citrate has a high bioavailability of 80-90% [24] and is present in standard rodent food. Possibly, the human patient with biallelic inactivating mutations in ANKH had a diet that was low in citrate, whereas part of the citrate detected in plasma of Ank ank/ank mice comes from dietary sources.…”

Section: Plos Geneticsmentioning

confidence: 99%

The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP

et al. 2020

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The membrane protein ANKH was known to prevent pathological mineralization of joints and was thought to export pyrophosphate (PPi) from cells. This did not explain, however, the presence of ANKH in tissues, such as brain, blood vessels and muscle. We now report that in cultured cells ANKH exports ATP, rather than PPi, and, unexpectedly, also citrate as a prominent metabolite. The extracellular ATP is rapidly converted into PPi, explaining the role of ANKH in preventing ankylosis. Mice lacking functional Ank (Ank ank/ank mice) had plasma citrate concentrations that were 65% lower than those detected in wild type control animals. Consequently, citrate excretion via the urine was substantially reduced in Ank ank/ ank mice. Citrate was even undetectable in the urine of a human patient lacking functional ANKH. The hydroxyapatite of Ank ank/ank mice contained dramatically reduced levels of both, citrate and PPi and displayed diminished strength. Our results show that ANKH is a critical contributor to extracellular citrate and PPi homeostasis and profoundly affects bone matrix composition and, consequently, bone quality.

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“…Existing alkalising agents are able to increase the urinary pH when compared to the corresponding placebo values but their duration of action is limited, requiring several daily administrations. The only alkalising therapy for which an extended release is claimed consists of a potassium citrate formulation (UROCIT-K tablets) but it has, however, been shown to exhibit a comparable profile to an immediate release liquid formulation of potassium citrate 20 . The period for which the urine pH was above 7.0 was short-lived and similar for both the liquid and the tablet formulation tested at the same dose (pH > 7.0 for only 3-4 h, approaching values observed in the placebo groups shortly thereafter).…”

Section: Discussionmentioning

confidence: 99%

Innovative prolonged-release oral alkalising formulation allowing sustained urine pH increase with twice daily administration: randomised trial in healthy adults

Guittet

Roussel‐Maupetit

Manso-Silván

et al. 2020

Sci Rep

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A multi-particulate fixed-dose combination product, consisting of a combination of two alkalising salts formulated as prolonged-release granules, ADV7103, was developed to obtain a sustained and prolonged alkalising effect. The specific release of both types of granules was shown in vitro through their dissolution profiles, which indicated that potassium citrate was released within the first 2-3 h and potassium bicarbonate up to 10-12 h after administration. The long-lasting coverage of ADV7103 was confirmed through a randomised, placebo-controlled, double-blind, two-period study, measuring its effect on urine pH in healthy adults (n = 16) at doses of alkalising agent ranging between 0.98 and 2.88 meq/kg/day. A significant increase of urine pH with a positive dose-response in healthy adult subjects was shown. Urine pH above 7 was maintained during 24 h with a dosing equivalent to 1.44 meq/kg twice a day, while urine pH was below 6 most of the time with placebo. The effect observed was non-saturating within the range of doses evaluated and the formulation presented a good safety profile. ADV7103 provided an effective prolonged release of alkalising salts to cover a 12-h effect with adequate tolerability and could afford a twice a day (morning and evening) dosing in patients requiring long-term treatment. Current alkalising treatments in adults and children generally consist of immediate-release forms of citrate or bicarbonate salts. The absorption of the actives is rapid, generating a peak of high alkaline load, and a short-lived effect. These treatments are characterized by inconvenient dosing schemes (3-6 daily doses), difficult day and night coverage and a jerky action leading to a variable efficacy, gastro-intestinal discomfort, and bad taste, which may result in poor acceptability and compliance 1,2. After oral administration, citrate undergoes oxidative metabolic breakdown to carbon dioxide (CO 2) or bicarbonate. Consequently, a basifying effect is associated with its metabolism 3. This salt is mainly absorbed under its divalent form (pH 4.8-6.4), and is thus known to have an absorption window limited to the upper side of the small intestine (duodenum, early part of the jejunum) 4. At physiological blood pH (7.4), citrate is entirely ionized in its trivalent form. Most of the citrate in the blood circulates unbound at relatively low (0.05 to 0.3 mmol/l) concentrations and the remaining quota is bound to calcium, potassium and sodium 5. In contrast, oral bicarbonate is absorbed all over the gastro-intestinal tract, independently of the local pH. A massive elimination of bicarbonate could occur in the stomach, since it neutralizes gastric acid with the production of CO 2 eliminated by the respiratory route. The remaining bicarbonate not involved in that reaction is rapidly absorbed by the intestinal mucosa 6-8. In order to maintain a sustained alkalising effect over 12 h with a good safety profile, ADV7103, a new prolonged-release oral formulation, was designed to maximise absorption of the active substances. ...

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Bioavailability of Citrate from Two Different Preparations of Potassium Citrate

Cited by 13 publications

References 5 publications

In vitro anti-lithogenic activity of lime powder regimen (LPR) and the effect of LPR on urinary risk factors for kidney stone formation in healthy volunteers

In vitro anti-lithogenic activity of lime powder regimen (LPR) and the effect of LPR on urinary risk factors for kidney stone formation in healthy volunteers

The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP

Innovative prolonged-release oral alkalising formulation allowing sustained urine pH increase with twice daily administration: randomised trial in healthy adults

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