Neutralization of Acidic Tumor Microenvironment (TME) with Daily Oral Dosing of Sodium Potassium Citrate (K/Na Citrate) Increases Therapeutic Effect of Anti-cancer Agent in Pancreatic Cancer Xenograft Mice Model.

Extracellular pH (pHe) of tumor cells is characteristic of tumor microenvironment (TME). Acidic TME impairs the responses of tumors to some anti-cancer chemotherapies. In this study, we showed that daily oral dosing of sodium potassium citrate (K/Na citrate) increased blood HCO3- concentrations, corresponding to increase of HCO3- concentrations and pHs in urine, and neutralized the tumor pHe. Neutralization of acidic TME by alkaline substance like HCO3-, an active metabolite of K/Na citrate, well potentiated the therapeutic effect of anticancer agent TS-1®, an orally active 5-fuluoro-uracil derivative, in Panc-1 pancreatic cancer-xenograft murine model. Neutralization of acidic TME by using an alkaline K/Na citrate is a smart approach for enhancement of the therapeutic effects of anticancer agents for pancreatic cancer in the end stage.

Superior calcium bioavailability of effervescent potassium calcium citrate over tablet formulation of calcium citrate after Roux-en-Y gastric bypass.

BACKGROUND: Calcium supplementation is commonly recommended for patients after Roux-en-Y gastric bypass to avert bone loss. To test the hypothesis that effervescent (liquid) potassium-calcium-citrate (PCC) might be more bioavailable than a tablet formulation of calcium citrate (Citracal Petite), the present study compared a single dose response of the 2 compounds. The present study was conducted at the University of Texas Southwestern Medical School at Dallas. METHODS: A total of 15 patients who had undergone Roux-en-Y gastric bypass were included in a 2-phase, crossover, randomized study comparing the single-dose bioavailability of PCC versus Citracal Petite. After following a restricted diet for 1 week, the participants ingested either a single dose of 400 mg elemental calcium as PCC or Citracal Petite. Sequential serum and urine samples were collected for a 6-hour period after the dose and analyzed for calcium, parathyroid hormone, and acid-base parameters. RESULTS: Compared with citracal petite, PCC significantly increased the serum calcium concentrations at 2, 3, and 4 hours after the oral load. The peak to baseline variation and increment in serum calcium (area under the curve) were significantly greater after PCC (P = .015 and P = .002, respectively). Concurrently, the baseline to nadir variation and decrement in serum parathyroid hormone (area over the curve) were significantly greater after PCC (P = .004 and P = .005, respectively). Moreover, compared with Citracal Petite, PCC caused a significantly greater increment in urinary citrate (P < .0001) and potassium (P = .0004) and a significantly lower increase in urinary ammonium (P = .045). CONCLUSION: In patients who have undergone Roux-en-Y gastric bypass, PCC was superior to Citracal Petite in conferring bioavailable calcium and suppressing parathyroid hormone secretion. PCC also provided an alkali load.

A new method for plasma citrate determination by reversed-phase high-performance liquid chromatography after ultrafiltration extraction: an example for bioequivalence evaluation of a medicinal endogenous substance.

Bioequivalence studies of pharmaceutical preparations of medicinal endogenous substances are generally lacking, as the endogenous background is the main obstacle for both experimental design and drug analysis. We conducted a single-dose, self-control, 3-period crossover study to evaluate the bioequivalence of a sustained-release versus an immediate-release preparation of potassium citrate for the treatment of urinary tract stones. This study included a placebo period to monitor the dynamics of endogenous plasma citrate, which could therefore be subtracted during the data processing. Notably, a new convenient method for plasma citrate determination utilizing ultrafiltration extraction and direct reversed-phase high-performance liquid chromatography (HPLC) was successfully applied in the study after validation. To our knowledge, this is the first report using simple reversed-phase HPLC to analyze plasma citrate, and ultrafiltration also significantly simplified the plasma extraction procedure. HPLC was performed using an ODS column, with acetonitrile and 0.02 mol/l sulfuric acid (3:97 v/v) as the mobile phase and ultraviolet detection at 210 nm. Results showed linearity from 10 to 200 microg/ml, an extraction recovery of more than 90% and analysis variability within 15% for additive citrate. The concentration of dog endogenous plasma citrate was determined to be about 30-40 microg/ml. The sustained-release preparation was bioequivalent to the immediate-release preparation in terms of the extent of absorption, but it could not achieve full effects due to a tmax issue.

[Therapeutic use of potassium citrate]. / Terapeutyczne zastosowania cytrynianu potasu.

Therapeutic indications of potassium citrate include: 1. Oxaluric renal stone disease and some cases of uric acid stone disease. Prevention of stone formation in patients with renal polycystic disease. Prevention of stone relapse after ESWL or lithotomy; 2. Distal renal tubular acidosis complicated by hypercalciuria, mainly in children. 3. Renal hypercalciuria and hyperoxaluria. 4. Prevention of renal complications at the time of glaucoma treatment with acetazolamide. 5. Potassium supplementation during treatment of hypertension. Potassium citrate is usually contraindicated in the case of: 1. Urinary tract infection. 2. Struvite renal stone disease. 3. Hyperpotassemia and advanced chronic renal failure. 4. Peptic ulcer or gastritis. 5. Gastrointestinal bleeding. 6. Disorders of coagulation, crural varices. 7. Metabolic alkalosis. Potassium citrate, when used at therapeutic doses, is to be considered as quite safe. The average daily dose even if admitted as a single dose day engages 60-75% of free renal capacity for potassium excretion. Physiologic and therapeutic citrate concentration in urine exceeds much those available for other inhibitors. The therapeutic dose does not induce any significant changes in any biochemical or endocrine parameter of blood except mild transient metabolic alkalosis. The decrease of urine calcium and increase in oxalate calcium phosphate excretion is observed. In hypo-cytriaturic patients the response to therapeutic dose of citrate is smaller. One-year remission of stone disease is observed in 70-75% cases.