Interaction between Bisphosphonates and Mineral Water: Study of Oral Risedronate Absorption in Rats

Abstract

Bisphosphonates are antiosteoporotic agents prescribed for patients with osteoporosis. Drug package inserts for bisphosphonate supplements indicate that their bioavailability is reduced by high levels of metal cations (Ca 2 , Mg 2 , etc.). However, standards for these cations in water used for taking risedronate have not been defined. Here, we examined the effect of calcium and magnesium in mineral waters on the bioavailability of the third-generation bisphosphonate, risedronate, following oral administration in rats. As risedronate is unchanged and eliminated renally, risedronate absorption was estimated from the amount excreted in the urine. Risedronate was dissolved in mineral water samples and administered orally at 0.35 mg/ kg. Urine samples were collected for 24 h after dosing. Risedronate was extracted from urine using ion-pair solid-phase cartridges and quantified by HPLC with UV detection (262 nm). Cumulative recovery of risedronate was calculated from the amount excreted in the urine. Key words risedronate; mineral water; drug interaction; urine excretion; rat Osteoporosis is a systemic disease characterized by reduced bone mass and structural deterioration of bone tissue, leading to an increased risk of fracture. According to the 2011 Guidelines for the Treatment of Osteoporosis, the number of patients with osteoporosis in the rapidly aging population of Japan is increasing and is now estimated at about 13 million. 1)The occurrence of a fracture significantly impacts a person's daily activities, so pharmacotherapy for the prevention of osteoporosis is recommended for patients who are at high risk of bone fracture. A variety of drugs are available for treating osteoporosis, including calcium agents, active vitamin D 3 , raloxifene, and bisphosphonates (BPs). BPs exhibit particularly potent bone resorption inhibitory activity and are therefore the first-choice drug for treating osteoporosis. 1)Because they inhibit resorption and thus increase bone mineral density, BPs play an important role in treating postmenopausal osteoporosis. The resorption-inhibiting activity of risedronate, a third-generation BP, is reported to be approximately 3000 times that of etidronate, a first-generation BP.2) Recently, risedronate began to be marketed for once per month (75 mg), in addition to daily (2.5 mg) and weekly (17.5 mg) dosing.The variety of mineral waters sold and consumed in Japan has increased in recent years. Annual consumption of mineral water per person in Japan was 25.7 L in 2014 (approximately 3 times that of 15 years ago).3) The consumption of mineral waters in Japan is predicted to increase further in coming years. For orally administered BPs, the package inserts advise patients and health care workers that the bioavailability of the drug may be reduced when taken with mineral waters containing high levels of metal cations (Ca 2+ , Mg 2+, etc.), as a result of chelation (Ajinomoto Co., Inc., Actonel ® package insert [2013/2]). As the hardness of a mineral water depends on its calcium and magnesium conten...

Effects of Low- and High-Mineral Content Water on the Relative Bioavailability of a Coformulated Abacavir/Dolutegravir/Lamivudine Dispersible Tablet in Healthy Adults

“…The test formulation was composed of a novel, dispersible, FDC preparation that contained 4 tablets of abacavir 150 mg/dolutegravir 10 mg/lamivudine 75 mg mixed with 3.0 mg/mL of acesulfame potassium, 1.2 mg/mL of sucralose, and 1.2 mg/mL of strawberry-cream flavor in 40 mL of either high-mineral content water (calcium, 468 mg/L; magnesium, 74.5 mg/L; Contrex, Nestlé Waters, Vevey, Switzerland) or purified, zero-mineral content water. 15 Participants were randomized (1:1:1:1:1) to 1 of 5 treatment groups over 5 dosing periods as follows (Figure, Supplemental Digital Content 1, http://links.lww.com/QAI/B218 , which illustrates the study design): reference treatment of abacavir 600 mg/lamivudine 300 mg plus 4 tablets of dolutegravir 10 mg administered with 200–250 mL of purified, zero-mineral content water without dispersion (tablets were nondispersible, film-coated); abacavir/dolutegravir/lamivudine dispersed in high-mineral content water and administered immediately; abacavir/dolutegravir/lamivudine dispersed in high-mineral content water with administration delayed for 30 minutes; abacavir/dolutegravir/lamivudine dispersed in purified, zero-mineral content water and administered immediately; and abacavir/dolutegravir/lamivudine dispersed in purified, zero-mineral content water with administration delayed for 30 minutes. All treatments were orally administered in the morning on an empty stomach, and food intake was prohibited for 4 hours following administration.…”

Metabolic Syndrome Features: Is There a Modulation Role by Mineral Water Consumption? A Review

“…Additionally, besides inflammation, a strong physiological/cellular link between a rising intracellular ratio of calcium to magnesium and aspects of metabolic syndrome, including hypertension, hyperinsulinemia, insulin resistance and left ventricular cardiac hypertrophy, has been described [170]. Considering that postmenopausal women were included in some of the studies discussed in this review (as for example in [73]) and menopause is a risk factor for osteoporosis [171], the consumption of mineral waters with calcium may impair bisphosphonates bioavailability [37,172].…”

Optimal Dosing Regimen of Osteoporosis Drugs in Relation to Food Intake as the Key for the Enhancement of the Treatment Effectiveness—A Concise Literature Review

“…The results of preclinical studies indicated that alendronate and risedronate absorption may decrease with the increasing concentration of calcium in mineral water used for drug administering [30,31]. As instructed by prescribing guidelines, oral bisphosphonates are recommended to be taken with tap water, to minimize the risk of malabsorption caused by calcium and other cations present in mineral and spring waters.…”