American Journal of Kidney Diseases
Volume 34 � Number 1 � July 1999
Copyright � 1999 W. B. Saunders Company
ORIGINAL INVESTIGATIONS
Effect of Potassium Magnesium Citrate on Thiazide-Induced Hypokalemia and Magnesium Loss
- Lisa A. Ruml MD
- Charles Y.C. Pak MD
From the Northwest Jersey Medical Associates, PA; and the Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX.
Received August 25, 1998;
accepted in revised form January 29, 1999.
Supported in part by grants no. PO1-DK20543 and M01RR00633 from the National Institutes of Health, Bethesda, MD.
Address reprint requests to Lisa A. Ruml, MD, 400 South Main St, Suite 2, Wharton, NJ 07885. E-mail: laruml@pol.net
� 1999 by the National Kidney Foundation, Inc. 0272-6386/99/3401-0014$3.00/0
The study was performed to ascertain the value of potassium magnesium citrate, magnesium citrate, and potassium citrate in overcoming thiazide-induced hypokalemia and magnesium loss. Sixty-two healthy subjects were first administered hydrochlorothiazide, 50 mg/d. After 3 weeks of thiazide treatment (or earlier for potassium level 
3.5 mEq/L), they were randomized to receive one of three drugs while continuing to receive thiazide: potassium magnesium citrate (49 mEq of potassium, 24.5 mEq of magnesium), magnesium citrate (24.5 mEq/d of magnesium), or potassium citrate (49 mEq/d of potassium). Outcome measures were changes in serum potassium and magnesium levels and urinary potassium, magnesium, pH, and citrate values. All three drugs increased serum potassium concentration compared with that resulting from thiazide alone. Potassium magnesium citrate increased serum potassium levels from 3.3 � 0.2 to 3.8 � 0.3 mEq/L (P < 0.001), potassium citrate increased serum potassium levels from 3.4 � 0.4 to 3.9 � 0.3 mEq/L (P < 0.001), and magnesium citrate from 3.4 � 0.4 to 3.7 � 0.3 mEq/L (P < 0.001). Potassium magnesium citrate led to a significant increase in urinary magnesium levels by the third week of supplementation (from 120 � 34 to 149 � 58 mg/d; P < 0.01) and produced a small but significant increase in serum magnesium level. Magnesium citrate significantly increased 24-hour urinary magnesium after the first week of supplementation and maintained this increase throughout the study. Potassium magnesium citrate and potassium citrate, but not magnesium citrate, significantly increased urinary pH and citrate values. Potassium magnesium citrate not only corrects thiazide-induced hypokalemia, but also may avert magnesium loss while providing an alkali load.
� 1999 by the National Kidney Foundation, Inc.
INDEX WORDS:
- Potassium magnesium citrate;
- hypokalemia;
- thiazide;
- magnesium depletion.
THIAZIDE DIURETICS have long been used to treat hypertension, volume overload, and edematous states. More recently, they have been used for the medical prevention of hypercalciuric nephrolithiasis.[1] A well-known side effect of thiazide use with important clinical consequences is the enhanced renal excretion of potassium and magnesium, leading to hypokalemia and hypomagnesemia. [2] Thiazide-induced hypokalemia can lead to muscle weakness and cramping, lethargy, and serious cardiac arrhythmias, particularly in older subjects. Arrhythmias may develop more frequently when hypomagnesemia is present. [3] [4] When thiazides are used in patients with hypercalciuric nephrolithiasis, their beneficial hypocalciuric effect may be negated by a reduction in urinary citrate, an important inhibitor of calcium stone formation.[5]
Although potassium chloride can prevent and reverse the hypokalemia induced by thiazide diuretics, it does not prevent the hypomagnesemia that may coexist. Likewise, potassium citrate used in conjunction with thiazide diuretics in patients with nephrolithiasis may prevent hypokalemia and hypocitraturia, but does not prevent increased renal magnesium losses. Potassium magnesium citrate was formulated to prevent both the hypokalemia and hypomagnesemia that may result from thiazide use, as well as avert hypocitraturia in stone-forming patients receiving thiazide for the control of hypercalciuria. This compound has already been shown to be effective in the prevention of calcium oxalate stone formation.[6]
This study of healthy subjects examines the efficacy of potassium magnesium citrate in preventing thiazide-induced hypokalemia and magnesium loss in comparison with potassium citrate or magnesium citrate.
MATERIALS AND METHODS
The study was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center (Dallas, TX). After informed consent was obtained, participants were questioned regarding their past medical history and underwent laboratory screening that included a serum chemistry panel, complete blood count, 24-hour urine analysis, and electrocardiogram. Participants were excluded from beginning the study if they had evidence of hypokalemia or hyperkalemia (serum potassium <3.5 or >5.5 mEq/ L), hypomagnesemia or hypermagnesemia (magnesium <1.2 or >2.0 mEq/L), creatinine clearance less than 0.6 mL/min/ kg, or an arrhythmia. They could have no history of heart or renal disease, chronic diarrhea, or active or recurrent peptic ulcer disease. Participants could not be receiving potassium or magnesium supplements or medications that could alter potassium or magnesium metabolism.
All participants underwent two phases of study, composed of a thiazide phase (1 to 3 weeks) followed by a supplement phase (3 weeks). Throughout both phases, subjects were instructed to follow a diet containing approximately 100 mEq of sodium, 40 to 60 mEq of potassium, and 160 to 200 mg of magnesium daily; they were also to drink at least 3 L of fluid daily. During the thiazide phase, participants were administered hydrochlorothiazide (HCTZ), 50 mg each morning. They were then seen weekly for a measurement of their serum potassium level. If hypokalemic symptoms developed, they were seen sooner. When the serum potassium level decreased to 3.5 mEq/L or less, subjects proceeded to the supplement phase and were randomized in a double-blinded fashion to receive potassium magnesium citrate, potassium citrate, or magnesium citrate, along with HCTZ, 50 mg/d. Subjects who developed hypokalemia were randomly allocated into one of the three treatment groups. They were then additionally stratified within each treatment group according to the degree of hypokalemia that developed (potassium >3.2 mEq/L or 3.2 mEq/L) and sex. Participants who did not develop hypokalemia after 3 weeks on HCTZ therapy were randomized into one of the three treatment groups to begin the supplement phase, with additional stratification according to sex.
During the supplement phase, all subjects received 7 tablets of the code medication, with 4 tablets after breakfast and 3 tablets after dinner, while continuing to receive HCTZ, 50 mg, each morning for 3 weeks. Subjects in group 1 received potassium magnesium citrate containing 49 mEq of potassium, 24.5 mEq of magnesium, and 73.5 mEq of citrate daily. Subjects in group 2 received potassium citrate containing 49 mEq of potassium and 49 mEq of citrate daily. Subjects in group 3 received magnesium citrate containing 24.5 mEq of magnesium and 24.5 mEq of citrate daily.
Potassium magnesium citrate contained 7 mEq of potassium, 3.5 mEq of magnesium, and 10.5 mEq of citrate per tablet. It is an investigational drug (Investigational New Drug 36,276, K-Mag) prepared by Mission Pharmacal Company (San Antonio, TX); University of Texas Southwestern Medical Center is the sponsor. Magnesium citrate contained 3.5 mEq of magnesium and citrate per tablet, and potassium citrate contained 7 mEq of potassium and citrate per tablet. Mission Pharmacal Company also prepared these medications so they could be identical in appearance. The three code drugs were identified by lot number only.
Subjects were followed up weekly in an outpatient setting. At each visit, a sitting blood pressure was obtained, and a venous blood sample was drawn for potassium and magnesium levels. A 24-hour urine sample was collected for potassium, magnesium, pH, and citrate. Stool was examined for occult blood before the study and at the end of the third week of supplementation using the Hemoccult test (SmithKline Diagnostics, Inc., Philadelphia, PA). A side-effect profile was obtained by using a questionnaire that addressed 14 gastrointestinal side effects and 4 other symptoms of hypokalemia or volume depletion. Each side effect was rated from 1 (none) to 4 (>7 episodes/wk) for frequency and 1 (none) to 4 (severe) for severity. Thus, the lowest score was 1 and highest score was 4 for each symptom. For all gastrointestinal symptoms, the lowest possible cumulative score was 14 and the highest was 56. For all other symptoms, the lowest score was 4 and highest 16.
Serum potassium was measured by using an ion-specific electrode, and serum magnesium by atomic absorption spectrophotometry in the laboratory of the General Clinical Research Center. Urinary potassium was analyzed by flame photometry, magnesium by atomic absorption spectrophotometry, and citrate using the citrate lyase method in the Mineral Metabolism Laboratory. Both laboratories have a certificate of approval for assay validation of these tests from the Health Care Financing Administration.
Statistical Analysis
For serum and urine parameters, repeated-measures analysis of variance with a grouping factor for the three treatments and a repeated factor for five measurements (phases: pre, last week of HCTZ, week 1, week 2, and week 3) was used to assess differences in response to the three treatments. An interaction between type of treatment and week of treatment would indicate that the responses to the different treatments are not the same. Because significant interactions between treatment group and phase were found, repeated-measures analysis of variance models were used for pairwise between-group comparisons (eg, potassium magnesium citrate v magnesium citrate, potassium magnesium citrate v potassium citrate, and potassium citrate v magnesium citrate) using the difference from the HCTZ phase. Within a treatment group, multiple comparisons were made using paired t-tests to compare the pre, week 1, week 2, and week 3 phases to the last thiazide phase. For both the pairwise analysis of variance models and t-tests, the 0.01 level of significance was used to adjust for multiple testing.
For side-effect frequency and severity scores, Wilcoxon's signed-rank test was used for comparisons with thiazide within groups, and the exact Wilcoxon's rank-sum statistic was used for comparing potassium magnesium citrate with magnesium citrate or potassium citrate. The 0.05 level of significance was used for these comparisons to avoid a type II error.
Results are expressed as mean � SD. Analyses were performed by using SAS version 6.12 (SAS Institute, Cary, NC).
RESULTS
Sixty-eight subjects (26 men, 42 women) satisfied all entry and exclusion criteria and began the study. Six subjects (two men, four women) began thiazide treatment but withdrew before entering the supplement phase. Of these six subjects, two were noncompliant in taking medications and in collecting urine, based on pill counts and 24-hour urinary creatinine level, respectively. Three subjects had to leave town and could not return for a scheduled visit, and one was instructed to stop the study by her private physician because of an upper respiratory infection. The 62 remaining subjects completed both phases of the study.
The demographics of the 62 subjects allocated to the three study groups are listed in Table 1 . Twenty subjects were randomized to the potassium magnesium citrate group (12 women, 8 men), 21 to the potassium citrate group (13 women, 8 men), and 21 to the magnesium citrate group (13 women, 8 men). There was no significant difference in age, weight, height, or woman-man ratio among the groups, although the mean body weight of the potassium magnesium citrate group was greater. Biochemically, the three groups did not differ significantly in their serum and urine potassium and magnesium levels, creatinine clearance, or urinary pH. Baseline urinary citrate level was slightly less in the potassium citrate group compared with the potassium magnesium citrate group (576 � 270 v 766 � 271 mg/d, respectively, P = 0.03); however, these values were well within the normal range.
| Potassium Magnesium Citrate | Magnesium Citrate | Potassium Citrate | |
|---|---|---|---|
| No. of patients | 20 | 21 | 21 |
| Sex (women/men) | 12/8 | 13/8 | 13/8 |
| Age (y) | 34.9 � 9.9 | 32.1 � 9.1 | 30.9 � 8 |
| Weight (kg) | 84 � 20 | 79 � 22 | 74 � 18 |
| Height (cm) | 170 � 9 | 168 � 11 | 169 � 9 |
| Serum | |||
| K (mEq/L) | 4.2 � 0.3 | 4.1 � 0.3 | 4.1 � 0.3 |
| Mg (mEq/L) | 2.1 � 0.2 | 2.0 � 0.2 | 2.1 � 0.2 |
| Urinary | |||
| K (mEq/d) | 61 � 24 | 56 � 22 | 60 � 19 |
| Mg (mg/d) | 111 � 38 | 101 � 35 | 114 � 40 |
| pH | 6.08 � 0.45 | 6.06 � 0.35 | 6.12 � 0.43 |
| Citrate (mg/d) | 766 � 271 | 658 � 291 | 576 � 270 * |
| Endogenous Cr clearance (mL/min) | 119 � 35 | 117 � 31 | 112 � 35 |
| Abbreviation: Cr, creatinine; K, potassium; Mg, magnesium. | |||
There was no significant difference in baseline mean arterial pressure (MAP) among the three groups ( Table 2 ). MAP decreased and remained below baseline in the potassium magnesium citrate group after thiazide therapy was begun. In the potassium citrate group, MAP decreased after thiazide therapy began, but was significantly less than baseline only after the third supplementation week. In the magnesium citrate group, MAP was not less after thiazide treatment, but was slightly but significantly less after the first and second supplement weeks.
| Potassium Magnesium Citrate | Magnesium Citrate | Potassium Citrate | |
|---|---|---|---|
| Pretreatment | 95 � 8 | 86 � 10 | 85 � 10 |
| Last week of thiazide alone | 87 � 9 * | 85 � 10 | 81 � 9  |
| Week 1 treatment phase | 86 � 9 * | 82 � 10 |
82 � 10 |
| Week 2 treatment phase | 86 � 9 * | 84 � 10 |
82 � 10 |
| Week 3 treatment phase | 89 � 8 * | 87 � 9 | 78 � 7 |
| Change from pretreatment | |||
| Week 1 treatment phase | -9 � 10 | -4 � 8 | -3 � 9 |
| Week 2 treatment phase | -8 � 10 | -4 � 8 | -3 � 11 |
| Week 3 treatment phase | -5 � 8 | 0 � 9 | -7 � 7 � |
P < 0.05, significant difference v pretreatment.P < 0.001, significant difference v pretreatment.�P < 0.01, the only significant difference between groups was at week 3 between magnesium citrate and potassium citrate.
Biochemical Changes in Serum
Baseline serum potassium levels decreased to 3.5 mEq/L or less in 48 subjects (77%) after treatment with HCTZ alone (18 subjects [90%] in the potassium magnesium citrate group; 14 subjects [67%] in the magnesium citrate group; and 16 subjects [76%] in the potassium citrate group). Data analyses were performed in the participants who developed hypokalemia, as well as all subjects. Because qualitatively similar findings were obtained, data for all subjects are reported here.
Subjects experienced an average decrease in serum potassium level of 0.7 to 0.9 mEq/L after beginning HCTZ. The decline was significant in all three groups (P < 0.001). After the first week of supplementation, there were significant increases in serum potassium level in all three groups ( Fig 1 ): from 3.3 � 0.2 to 3.8 � 0.3 mEq/L in the potassium magnesium citrate group (P < 0.001); from 3.4 � 0.4 to 3.9 � 0.3 mEq/L in the potassium citrate group (P , 0.001); and from 3.4 � 0.4 to 3.7 � 0.3 mEq/L in the magnesium citrate group (P < 0.001). These increases were sustained in weeks 2 and 3 of the supplement phase in all three groups. For all serum potassium determinations from all subjects during 3 weeks of supplementation, serum potassium concentration was greater than 3.5 mEq/L in 88.3% of determinations in the potassium magnesium citrate group, 85.7% of determinations in the magnesium citrate group, and 82.5% of determinations in the potassium citrate group.
Figure 1. Mean serum potassium levels in all patients completing the study. Abbreviations: K, potassium; TZ, thiazide; Code Rx, treatment with potassium magnesium citrate, magnesium citrate, or potassium citrate; vertical bars, mean � SD. P < 0.001 for treatment v last week of TZ.
Serum magnesium levels did not change after treatment with HCTZ alone in any group ( Fig 2 ). After the first week of supplementation, serum magnesium levels increased slightly but significantly in both the potassium magnesium citrate (2.0 � 0.2 to 2.2 � 0.2 mEq/L; P = 0.009) and the magnesium citrate groups (2.1 � 0.1 to 2.2 � 0.2 mEq/L; P = 0.013), but not in the potassium citrate group. The significance was maintained after the second week of supplementation only in the potassium magnesium citrate group. There was no significant change in any group after the third week of supplementation.
Figure 2. Mean serum magnesium levels in all patients completing the study. Abbreviations: Mg, magnesium; TZ, thiazide; Code Rx, treatment with potassium magnesium citrate, magnesium citrate, or potassium citrate; vertical bars, mean � SD. *P < 0.05. **P < 0.01 for treatment v last week of TZ.
The changes in serum potassium and magnesium levels from the HCTZ phase to the supplement phase were not significantly different among the three groups.
Changes in Urinary Biochemistry
Urinary potassium level increased slightly with HCTZ, but not significantly ( Table 3 ). Urinary potassium levels increased significantly from HCTZ alone during all 3 weeks of supplementation with potassium magnesium citrate and potassium citrate, but not in the magnesium citrate group at any week. There were significantly lower urinary potassium levels in the magnesium citrate group compared with both the potassium magnesium citrate and the potassium citrate groups during all 3 weeks of supplementation (P, 0.02 to 0.0007).
| Potassium Magnesium Citrate | Magnesium Citrate | Potassium Citrate | |
|---|---|---|---|
| Urinary potassium (mEq/d) | |||
| Pretreatment | 61 � 24 | 56 � 22 | 60 � 19 |
| Last week of thiazide alone | 67 � 25 | 62 � 25 | 65 � 23 |
| Week 1 treatment phase | 83 � 23 * | 56 � 23 | 96 � 28 |
| Week 2 treatment phase | 87 � 35 * * | 52 � 21 | 101 � 32 |
| Week 3 treatment phase | 94 � 32 |
55 � 20 | 94 � 25 |
| Urinary magnesium (mg/d) | |||
| Pretreatment | 111 � 38 | 101 � 35 | 114 � 40 |
| Last week of thiazide alone | 120 � 34 | 94 � 24 | 106 � 51 |
| Week 1 treatment phase | 132 � 54 | 136 � 53 |
107 � 43 |
| Week 2 treatment phase | 128 � 50 | 143 � 46 |
118 � 42 |
| Week 3 treatment phase | 149 � 58 |
150 � 44 |
111 � 36 |
P < 0.01, significant difference v thiazide alone.P < 0.001, significant difference v thiazide alone.Urinary magnesium levels were not changed with HCTZ alone in any group, although there was a nonsignificant increase in the potassium magnesium citrate group and decrease in the other two groups ( Table 3 ). Magnesium citrate supplementation increased urinary magnesium levels from 94 � 24 to 136 � 53 mg/d after the first week (P < 0.001) and to 150 � 44 mg/d by the end of the third week of supplementation (P < 0.001). Urinary magnesium levels increased slowly in the potassium magnesium citrate group, reaching significance after the third week of supplementation (from 120 � 34 to 149 � 58 mg/d; P = 0.009). There was no change in the potassium citrate group. Among groups, there were significantly greater urinary magnesium levels in the magnesium citrate group compared with the potassium citrate group at all 3 weeks (P, 0.03 to 0.005). The difference in urinary magnesium levels between the potassium magnesium citrate and potassium citrate groups was less marked (P, 0.1 to 0.01). There was no significant difference in urinary magnesium levels between the magnesium citrate and potassium magnesium citrate groups in the first and third week, but the magnesium citrate group had a slightly greater value after the second week of supplementation (P = 0.01).
Urinary pH did not change significantly with HCTZ alone ( Fig 3 ). It increased significantly during each week of supplementation in both the potassium magnesium citrate and potassium citrate groups, but not in the magnesium citrate group. HCTZ treatment reduced urinary citrate levels in all groups; the decline was significant in the potassium magnesium citrate and potassium citrate groups ( Fig 4 ). Urinary citrate levels increased significantly during all 3 weeks in the potassium magnesium citrate and potassium citrate groups. There was a smaller, nonsignificant increase in the magnesium citrate group. The changes in urinary pH and citrate values from the HCTZ phase to the supplement phase were significantly different between potassium magnesium citrate and magnesium citrate groups (P < 0.001), but not between potassium magnesium citrate and potassium citrate groups.
Figure 3. Mean urinary pH for all patients completing the study. Abbreviations: TZ, thiazide; Code Rx, treatment with potassium magnesium citrate, magnesium citrate, or potassium citrate; vertical bars, mean � SD. P < 0.001 for treatment 1v last week of TZ.
Figure 4. Mean urinary citrate levels for all patients completing the study. Abbreviations: TZ, thiazide; Code Rx, treatment with potassium magnesium citrate, magnesium citrate, or potassium citrate; vertical bars, mean � SD. P < 0.001. **P < 0.01. *P < 0.05 for treatment v last week of TZ.
Safety and Other Results
During the thiazide phase, the individual gastrointestinal score was mainly 1.0 (lowest value) in all three groups. Individual scores for nongastrointestinal symptoms were mostly 1.1 or greater. During the supplement phase, individual scores either did not change or decreased. The cumulative score for all gastrointestinal symptoms was slightly greater than the lowest value of 14 and did not differ significantly between the thiazide and supplement phases in all three groups. The score for all nongastrointestinal symptoms during the thiazide phase was slightly but significantly greater than prethiazide treatment in the magnesium citrate group. This value was numerically less during the supplement phase than during the thiazide phase in all three groups, but the change was not significant. There was no significant difference in the frequency or severity of individual or all gastrointestinal and nongastrointestinal symptoms among the three groups.
No subject had a positive test for occult fecal blood. The compliance in taking test medications, obtained from pill counts, was 98% for HCTZ, 97% for potassium magnesium citrate, 95% for magnesium citrate, and 101% for potassium citrate.
DISCUSSION
The study was undertaken with the aim of comparing the efficacy of three citrate salts of potassium or magnesium in correcting thiazide-induced hypokalemia and averting magnesium loss in healthy subjects. Critical end points examined included clinical effects (changes in serum potassium and magnesium levels), pharmacokinetic effects (changes in 24-hour urinary potassium and magnesium levels as a measure of bioavailability), and pharmacodynamic effects (changes in urinary pH and citrate values). The study showed that all three salts (potassium magnesium citrate, potassium citrate, and magnesium citrate) were able to restore normal serum potassium levels in the majority of subjects, although only the first two salts contained potassium. The two magnesium-containing salts delivered absorbable magnesium (shown by an increase in urinary magnesium level) and led to a slightly but significantly greater serum magnesium concentration. Potassium magnesium citrate and potassium citrate, but not magnesium citrate at the dose administered, increased urinary pH and citrate values.
Potassium and magnesium deficiency are well-known consequences of treatment with thiazide and loop diuretics, such as HCTZ, chlorthalidone, furosemide, and perhaps indapamide.[2] Hypokalemia can lead to weakness, muscle cramping, and, more ominously, cardiac arrhythmias. Hypomagnesemia can exacerbate hypertension, cardiac arrhythmias, muscle weakness, and cardiac ischemia and cause hypocalcemia. Concomitant magnesium depletion in the setting of hypokalemia can also make potassium deficiency refractory to correction.[7] [8] The recognition of the need to replace both magnesium and potassium losses led us to test the utility of potassium magnesium citrate in this study.
Potassium magnesium citrate was effective in achieving all the critical end points examined. Serum potassium levels were maintained or restored to the normal range in 88.3% of the subjects receiving thiazide, and serum magnesium levels increased slightly in concert with an increase in urinary magnesium (after no change with thiazide alone), indirect evidence of a more positive magnesium balance. Because of an increase in urinary pH and citrate values as a result of the provision of alkali, potassium magnesium citrate should be especially useful in the sub-group of hypercalciuric patients with calcium nephrolithiasis treated with thiazide.
Although potassium citrate favorably influenced some of the critical end points studied, it was not as advantageous as potassium magnesium citrate because of the absence of magnesium. Whereas magnesium citrate was able to normalize serum potassium and increase urinary magnesium levels, one would expect a less positive potassium balance in this group compared with the two groups receiving the potassium salts. Moreover, at the same dose of magnesium as in potassium magnesium citrate, magnesium citrate was devoid of alkalinizing and citraturic effects.
Blood pressure tended to decline with thiazide treatment. It has been suggested that acute decreases in serum potassium level augment blood pressure in hemodialysis patients,[9] but the use of a thiazide diuretic could have opposed this effect on blood pressure. It appeared that the decline in blood pressure produced by thiazide was sustained during supplementation, particularly with potassium magnesium citrate.
The cellular transport and metabolism of magnesium are closely linked to those of potassium, with perturbations in magnesium producing substantial changes in serum and tissue potassium levels.[10] [11] These changes in potassium are believed to be caused by both a diminished influx and enhanced efflux to and from cells, both of which have been described.[12] [13] In the setting of magnesium depletion, hypokalemia can persist even in the presence of excess dietary potassium.[7] [14] Thus, the provision of magnesium alone by magnesium citrate may have ameliorated or corrected thiazide-induced hypokalemia by overcoming disturbances in cellular potassium transport.
Potassium bioavailability from potassium magnesium citrate and potassium citrate has been shown to be nearly complete.[15] [16] Thus, one would expect the increase in urinary potassium to reflect the dose administered once a steady-state is achieved. However, the increase shown in this study was 30 to 35 mEq/d in the potassium citrate group and only 16 to 27 mEq/d in the potassium magnesium citrate group, although 49 mEq of potassium were delivered with the medications daily. This finding could reflect increased total-body potassium retention as a result of the coadministered magnesium.[14]
Potassium magnesium citrate was well tolerated. It had a very low side-effect profile, which did not differ significantly from magnesium citrate or potassium citrate.
In summary, potassium magnesium citrate is effective in reversing hypokalemia and may improve magnesium balance in subjects receiving thiazide diuretics. It also increases urinary pH and citrate values, making it an effective drug for the prevention of the formation of uric acid and calcium oxalate stones.
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