Original Investigation
Comparison of Dietary Phosphate Absorption After Single Doses
of Lanthanum Carbonate and Sevelamer Carbonate in
Healthy Volunteers: A Balance Study
Patrick Martin, MD,1 Phillip Wang, PhD,1 Antoine Robinson, MSN, CRNP,1
Lynne Poole, MSc,2 Jeffrey Dragone, MS,1 Michael Smyth, FRCS, MRCGP,2 and
Raymond Pratt, MD1
Background: Lanthanum carbonate and sevelamer carbonate are noncalcium phosphate binders used to treat
hyperphosphatemia in patients with chronic kidney disease. This is the first study to compare phosphate absorption
from a standardized meal ingested with a typical clinical dose of these binders.
Study Design: Randomized open-label crossover study.
Settings & Participants: Healthy volunteers were confined to a clinical research center during 4 study
periods. Of 31 volunteers randomly assigned, 19 completed all treatments and 18 were analyzed in the
pharmacodynamic set (1 was excluded because of vomiting).
Intervention: Participants were assigned in random order to meal alone, meal plus lanthanum carbonate (1
tablet containing 1,000 mg of elemental lanthanum), and meal plus sevelamer carbonate (three 800-mg
tablets). The gastrointestinal tract was cleared, the meal was ingested (⫾ treatment), and rectal effluent was
collected. In a fourth period, volunteers repeated the study procedures while fasting.
Outcomes: The primary end point, net phosphate absorption, was analyzed using a mixed-effect linear
model.
Measurements: Phosphorus content of effluent and duplicate meal samples were measured using
inductively coupled plasma– optical emission spectroscopy.
Results: The standard meal contained ⬃375 mg of phosphate, 75% of which was absorbed (net absorption,
281.7 ⫾ 14.1 mg [adjusted mean ⫾ standard error]). Lanthanum carbonate decreased net phosphate
absorption by 45% (net absorption, 156.0 ⫾ 14.2 mg) compared with 21% (net absorption, 221.8 ⫾ 14.1 mg)
for sevelamer carbonate (P ⬍ 0.001). Lanthanum carbonate bound 135.1 ⫾ 12.3 mg of phosphate, whereas
sevelamer carbonate bound 63.2 ⫾ 12.3 mg, a 71.9-mg difference (95% CI, 40.0-103.8; P ⬍ 0.001). Per tablet,
this equates to 135 mg of phosphate bound with lanthanum carbonate versus 21 mg with sevelamer carbonate.
Limitations: A single-dose study.
Conclusions: In healthy volunteers, 1,000 mg of lanthanum carbonate decreased phosphate absorption by
45% compared with a 21% decrease with 2,400 mg of sevelamer carbonate.
Am J Kidney Dis. xx(x):xxx. © 2011 by the National Kidney Foundation, Inc.
INDEX WORDS: Chronic kidney disease; clinical trial; lanthanum carbonate; phosphate binder; sevelamer
carbonate.
A
n increased serum phosphorus level is associated
with increased morbidity and mortality in patients
with chronic kidney disease (CKD), including those not
yet requiring dialysis.1,2 Patient management strategies
to decrease serum phosphorus levels include dietary
phosphate restriction and provision of adequate dialysis
when renal replacement therapy is required. A cohort
study showed that sustained control of serum phosphorus levels to 3.5-5.5 mg/dL is a strong predictor of
improved survival in patients new to dialysis therapy.3
Unfortunately, dietary phosphate restriction and dialysis
often are insufficient to control serum phosphorus to
guideline levels, such as those recommended by KDOQI
(ie, the National Kidney Foundation’s Kidney Disease
Outcomes Quality Initiative) and the KDIGO (Kidney
Disease: Improving Global Outcomes) group, which are
3.5-5.5 mg/dL and ⬍4.6 mg/dL, respectively.4,5 Approximately 40% of patients on dialysis therapy still have
serum phosphorus levels ⬎5.5 mg/dL.6
Am J Kidney Dis. 2011;xx(x):xxx
There may be risks associated with trying to improve hyperphosphatemia through dietary restriction.
Data from patients on dialysis therapy have shown
that increasing protein intake while decreasing serum
phosphorus level is associated with a lower risk of
mortality compared with concurrent increases or decreases in both parameters or a decrease in protein
From 1Shire Pharmaceuticals, Wayne, PA; and 2Shire Pharmaceuticals, Basingstoke, UK.
Received July 13, 2010. Accepted in revised form November 17,
2010.
Trial registration: ClinicalTrials.gov; study number: NCT00875017.
Address correspondence to Patrick Martin, MD, Shire Pharmaceuticals, 725 Chesterbrook Blvd, Wayne, PA 19087-5637. E-mail:
pmartin@shire.com
© 2011 by the National Kidney Foundation, Inc.
0272-6386/$36.00
doi:10.1053/j.ajkd.2010.11.028
1
Martin et al
intake with an increase in serum phosphorus level.7
KDOQI recommends protein intake of 1.2 g/kg of
body weight per day for hemodialysis patients.8 Based
on an average phosphate content of 10-12 mg/g of
protein, a 70-kg patient consumes 84 g of protein and
840-1,008 mg/d of phosphate.5 Because 60%-80% of
ingested phosphate is absorbed from the gastrointestinal (GI) tract,9 a typical dialysis patient may absorb at
least 3,500 mg/wk of phosphate. Because thriceweekly hemodialysis typically removes 2,400 mg of
phosphate,5 a net positive phosphate balance of at
least 1,000 mg/wk may occur. It therefore is very
difficult to maintain a net neutral balance or induce a
net negative phosphate balance without dietary protein restriction or pharmacologic intervention. The
use of efficacious dietary phosphate binders may be
desirable to treat increased serum phosphorus levels
because they would allow patients on dialysis therapy
to maintain adequate protein intake and neutral phosphate balance.
Several phosphate binders are available for use by
patients with CKD. Calcium-based agents commonly
are prescribed for patients on dialysis therapy, but
high daily doses often are required, potentially increasing calcium load and the risk of vascular calcification.10,11 The current alternatives, non–calcium-based
lanthanum carbonate (Fosrenol; Shire Pharmaceuticals, www.shire.com) and sevelamer (Renagel and
Renvela; Genzyme Corp, www.genzyme.com), may
be associated with a lower risk of vascular calcification,12-14 and studies have shown an association with
improved survival when they are used compared with
calcium-based agents in a subset of patients on dialysis therapy who are older than 65 years.15,16
Knowledge of a patient’s dietary phosphate intake
and dialysis regimen combined with information about
the phosphate-binding capacity of phosphate binders
may allow tailoring of prescriptions to achieve decreases in serum phosphorus level and phosphate load
while maintaining adequate protein intake. Assessments of the relative phosphate-binding capacities of
lanthanum carbonate and sevelamer have been limited
to in vitro and animal studies17,18 and indirect clinical
comparisons versus the hydrochloride salt of sevelamer
using 24-hour urinary excretion of phosphorus to
estimate decreases in phosphate absorption.19,20 The
binding capacities of aluminum- and calcium-based
phosphate binders have been examined directly in a
previous study by Sheikh et al.21 In their study,
measurement of phosphorus in rectal effluent enabled
direct assessment of dietary phosphate absorption and
the phosphate-binding capacities of these agents. Use
of healthy volunteers allowed assessment of phosphate absorption without interference from physiologic factors associated with CKD and its treatment.
2
Using methods similar to that of Sheikh et al,21 the
study reported here directly compared the decrease in
dietary phosphate absorption and binding capacities
of lanthanum carbonate and sevelamer carbonate.
METHODS
Study Design
This open-label randomized crossover study was conducted in
the United States in accordance with International Conference on
Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use Good Clinical Practice guideline
E6,22 consistent with the Declaration of Helsinki. The study was
conducted on behalf of Shire Pharmaceuticals by an independent
study unit. Healthy male and female volunteers aged 19-45 years
with body mass index of 20.0-29.9 kg/m2 and serum 1,25dihydroxyvitamin D3 level ⬎30 pg/mL were included in the study.
Nonpregnant women of childbearing potential were required to
use appropriate methods of contraception during the study. Written
informed consent was obtained from all individuals.
The eligibility of volunteers was confirmed during a 28-day
screening period and reconfirmed at the start of each of 4 study
periods when participants underwent assessment of vital signs,
safety laboratory parameters, electrocardiography, and urinalysis.
Women of childbearing potential had to have had a negative
pregnancy test result.
At the start of study period 1, participants were randomly
assigned using a computer-generated list with a block size of 6 to 1
of 6 treatment sequences, each consisting of 4 periods separated by
a 7- to 14-day washout (Fig 1). In each of the first 3 periods,
participants received a meal standardized for phosphate content,
the standard meal plus lanthanum carbonate (a single tablet containing 1,000 mg of elemental lanthanum), or the standard meal plus
sevelamer carbonate (2,400 mg; three 800-mg tablets). Participants repeated the study procedures while fasting in the fourth
period. Five days after completion of the fasting period or early
withdrawal from the study, individuals were followed up to report
any ongoing concomitant medications or adverse events (AEs) and
any new AEs or serious AEs.
Because studies suggesting a required dosage for sevelamer
carbonate are sparse, doses were chosen based on those typically
used in clinical trials of sevelamer hydrochloride and lanthanum
carbonate.11,14,23,24 The carbonate and hydrochloride forms of
sevelamer have been shown to be bioequivalent for the decrease in
serum phosphorus levels.25 Doses were consistent with the prescribing information.26,27
Dosing and Sample Collection
After admission to the clinical research center at the start of each
study period, participants received a clear-liquid dinner (broth,
Jell-O [Kraft Foods, www.kraftfoodscompany.com], and juice)
and then fasted (with access to only deionized water) until lunchtime of the following day, when they received the standardized
meal with or without phosphate-binder treatment. During the
fasting period, participants underwent the same procedures, but
did not consume the meal or phosphate binders.
Four hours before ingestion of the meal, the GI tract was cleared
by flushing with mannitol solution (3-4 L of solution D as described by Davis et al,28 administered using a nasogastric tube at
20-30 mL/min) until the stool was clear of solid material, confirmed visually by research center staff.
During the assigned periods, participants were administered
lanthanum carbonate or sevelamer carbonate with 250 mL of
deionized water (containing 10 g of the nonabsorbable marker
Am J Kidney Dis. 2011;xx(x):xxx
Phosphate Absorption: Lanthanum vs Sevelamer
Figure 1. A randomized open-label crossover study comparing absorption of dietary phosphate after doses of lanthanum carbonate
(LC; 1,000 mg of elemental lanthanum) or sevelamer carbonate (SC; 2,400 mg). Abbreviation: R, randomization.
polyethylene glycol) halfway through ingestion of the standard
meal. The meal was consumed within a 30-minute period.
Approximately 10 hours were allowed for digestion of the meal,
after which a second 4-hour GI wash was performed and the rectal
effluent was collected. No liquids other than deionized water were
consumed during treatment. Because participants underwent dosing and sample collection under the close supervision of the study
investigator, visual inspection of rectal effluent was deemed sufficient to confirm that the GI tract had been cleared. Given methods
similar to the study by Sheikh et al,21 which showed 99%-100%
recovery of polyethylene glycol, analysis of polyethylene glycol
levels in rectal effluent was thought to be unnecessary. Care was
taken to avoid contamination of the rectal effluent with urine.
Participants were required to remain resident in the research center
until 24 hours after dosing.
Standardized Meal
The standardized meal consisted of a broiled ground beef patty
(80 g; 90% lean meat, 10% fat) with Swiss cheese (30 g) and
french-fried potatoes (100 g). This meal was expected to contain
⬃429 mg of phosphate, based on reference data.29 Identical
duplicate meals were analyzed independently to determine the
actual phosphate content of meals.
Sample Preparation
Meal samples were ground and digested with concentrated nitric
acid (70%; 1 mL/1 g of sample) on a hot plate for 0.5-1.0 hours.
The resulting suspension was diluted with mannitol/electrolyte
solution and the final volume was recorded. Rectal effluent samples
were filtered and the residue was digested with concentrated nitric
acid (as per the meal samples) before being recombined with the
filtrate. The final volume (calculated based on weight and density
measurements) was recorded. Processed samples were frozen
(nominal ⫺20°C) in 50-mL aliquots for subsequent analysis.
Quantification of Phosphorus
The colorimetric technique for detection of phosphorus30 used
by Sheikh et al21 was unsuitable for use with lanthanum because
the assay can measure only free phosphate in solution. Although
the acid treatment used as part of the colorimetric assay effectively
dissociated the aluminum-phosphate complex, allowing accurate
assessment of phosphorus in the study by Sheikh et al,21 the same
procedure applied to lanthanum-containing samples resulted in
lower than expected phosphorus recovery. This may occur because
the lanthanum-phosphate complex is poorly soluble in acidic
solution. This is reflected by the low dissociation constant of
lanthanum phosphate calculated in previous in vitro studies.17
Am J Kidney Dis. 2011;xx(x):xxx
Therefore, an alternative method was validated to ensure accurate
measurement of phosphorus in rectal effluent samples.
Phosphorus concentrations were analyzed using an inductively
coupled plasma–optical emission spectroscopy (ICP-OES) assay.
This assay was able to accurately measure phosphorus in the
presence of the lanthanum-phosphate complex with recovery of
⬃100%. All samples, including those from meal-only and mealplus-sevelamer-carbonate treatments, therefore, were analyzed using ICP-OES.
Inductively Coupled Plasma–Optical
Emission Spectroscopy
Processed samples were analyzed for phosphorus using ICPOES in a mannitol/electrolyte matrix. Samples (3 mL) were
digested in concentrated nitric acid (2.5 mL) at 110°C for 1.5 hours
followed by concentrated hydrochloric acid (⬃38%, 2.5 mL) at
100°C for 30 minutes and then diluted to 50 mL using mannitol/
electrolyte solution. Scandium was added as an internal standard
and the suspension was vortexed before being introduced into the
ICP-OES system (4300 DV Optima Inductively Coupled Plasma–
Optical Emission Spectrometer; Perkin-Elmer, www.perkinelmer.
com). Calibration standards and quality control samples in mannitol/
electrolyte solution were digested and processed using the same
procedure as for study samples. Phosphorus and scandium were
monitored at wavelengths of 214.91 and 361.38 nm, respectively.
Phosphorus concentrations were obtained using the instrument
software. The amount of phosphorus was calculated from the
measured concentration and final volume recorded in the initial
preparation step. Investigators who assayed samples for phosphorus were blinded to treatment allocation.
Objectives
The primary objective was to compare the absorption of dietary
phosphate after a single dose of either lanthanum carbonate or
sevelamer carbonate. The primary end point to assess this objective was net phosphate absorption. Secondary objectives included
comparison of the dietary–phosphate-binding capacity of typical
clinical doses of lanthanum carbonate and sevelamer carbonate,
and assessment of the safety and tolerability of lanthanum carbonate and sevelamer carbonate.
The safety set consisted of individuals who received at least 1
dose of study drug and had at least 1 postdose safety assessment.
The pharmacodynamic set consisted of all individuals in the safety
set who provided all rectal effluent collections and completed all
study periods. Individuals who vomited during any of the study
periods were excluded from the pharmacodynamic set.
3
Martin et al
Net phosphate absorption and phosphate-binding capacity were
calculated according to the following equations. Net phosphate
absorption ⫽ phosphorus measured in standardized meal – (phosphorus measured in rectal effluent following meal only or meal
with binder administration – phosphorus in rectal effluent following fasting). Phosphate-binding capacity ⫽ phosphorus measured
in rectal effluent following meal with binder administration ⫺
phosphorus measured in rectal effluent following meal only.
Statistical analyses were performed using SAS, version 9.2
(www.sas.com). Data were analyzed using a standard mixed-effect
linear model with adjustment for sequence group, period, and
treatment as fixed effects; subject within sequence was included as
a random effect. The analysis used the pharmacodynamic set.
Fifteen volunteers were required to complete the study to ensure
80% power to detect a 42-mg difference in phosphate absorption
between lanthanum carbonate and sevelamer carbonate at the 5%
significance level (2 sided) assuming a standard deviation of 50
mg.
The study was not designed or powered to assess differences in
the safety or tolerability profiles of lanthanum carbonate and
sevelamer carbonate.
RESULTS
Thirty-one individuals were randomly assigned, 28
of whom received a dose of study drug and were
included in the safety set. Eighteen participants were
included in the pharmacodynamic set; reasons for
exclusion are shown in Fig 2. Most participants were
white (61%) and men (78%); mean age of the pharmacodynamic set was 26 ⫾ 6.8 (standard deviation)
years (Table 1).
Table 1. Participant Demographics for the Pharmacodynamic
Set
Parameter
Value
Sex
Men
Women
14 (78)
4 (22)
Race
White
Black
11 (61)
7 (39)
Ethnicity
Hispanic or Latino
Not Hispanic or Latino
4 (22)
14 (78)
Age (y)
Weight (kg)
BMI (kg/m2)
26 ⫾ 6.8
73 ⫾ 8.4
25 ⫾ 2.3
Note: Values shown as number (percentage) or mean ⫾
standard deviation.
Abbreviation: BMI, body mass index.
Mean phosphorus content of the meal and rectal
effluent samples after lanthanum carbonate or
sevelamer carbonate treatment and fasting are listed
in Table 2. Net phosphate absorption (adjusted mean
⫾ standard error) after receiving the meal without a
phosphate binder was 281.7 ⫾ 14.1 mg of phosphorus
(Fig 3). Net phosphate absorption was significantly lower
with lanthanum carbonate (156.0 ⫾ 14.2 mg of phosphorus) than with sevelamer carbonate (221.8 ⫾ 14.1 mg of
phosphorus); the difference in adjusted mean values was
⫺65.8 mg of phosphorus (95% confidence interval,
⫺96.0 to ⫺35.5; P ⬍ 0.001; Fig 3).
Lanthanum carbonate (1,000 mg of elemental lanthanum) bound 135.1 ⫾ 12.3 mg of phosphate (as
phosphorus), whereas sevelamer carbonate (2,400 mg)
bound 63.2 ⫾ 12.3 mg, a difference in adjusted mean
values of 71.9 mg (95% confidence interval, 40.0103.8; P ⬍ 0.001; Fig 4).
Safety and Tolerability
Treatment-emergent AEs during the meal-only study
period were limited to nausea, vomiting, headache,
and dizziness. AEs were similar during fasting, with
the addition of a single case of pruritic rash. During
sevelamer carbonate treatment, 1 participant had 2
treatment-emergent AEs (an arthropod sting and pruritus). No treatment-emergent AEs occurred during
lanthanum carbonate treatment.
Figure 2. Participant disposition. [Number] signifies treatment period (including the subsequent washout period). Abbreviations: AE, adverse event; GI, gastrointestinal.
4
DISCUSSION
Previous assessments of the relative phosphatebinding capacities of lanthanum carbonate and
sevelamer hydrochloride have been limited to in vitro
investigations,17 animal studies,18 and indirect cliniAm J Kidney Dis. 2011;xx(x):xxx
Phosphate Absorption: Lanthanum vs Sevelamer
Table 2. Phosphorus Content of Samples
Meal (mg)
Rectal Effluent (mg)
Study Period
Mean ⴞ SE
Range
Mean ⴞ SE
Range
Meal only
Meal plus lanthanum carbonate (1,000 mg of elemental
lanthanum)
Meal plus sevelamer carbonate (2,400 mg)
Fasting
374.3 ⫾ 4.0
377.1 ⫾ 3.1
349.8-401.4
349.8-401.4
151.0 ⫾ 7.5
279.7 ⫾ 17.6
105.0-206.2
141.0-405.3
375.0 ⫾ 4.0
—
349.8-401.4
212.4 ⫾ 9.3
60.9 ⫾ 4.1
144.0-285.4
31.3-94.4
Note: N ⫽ 18. Conversion factor for phosphorus in mg to mmoles, ⫻0.0323.
Abbreviation: SE, standard error.
cal comparisons using 24-hour urinary excretion of
phosphorus to estimate phosphate absorption.19,20 This
is the first study in humans to directly compare the
effects of lanthanum carbonate and recently introduced sevelamer carbonate on dietary phosphate absorption and allowed calculation of their in vivo
phosphate-binding capacities. These results validate
measurement of urinary phosphorus excretion as a
biomarker reflecting the effect of phosphate binders.19,20
The balance study reported by Sheikh et al21 directly assessed the phosphate-binding capacities of
aluminum carbonate and the citrate, acetate, and carbonate salts of calcium by measuring net phosphate
absorption after ingestion of a standardized meal
along with these phosphate binders. That study found
that aluminum carbonate and calcium acetate had
higher phosphate-binding capacities than calcium carbonate and calcium citrate. The method used by
Sheikh et al21 and in this study is most appropriate for
direct assessment of the binding capacities of phosphate binders because it measures phosphorus bound
to the binder (and hence removed in the rectal effluent).
We intended to use the same assay as Sheikh et al21
to directly compare the phosphate-binding capacities
Figure 3. Lanthanum carbonate significantly decreased net
phosphate absorption compared with sevelamer carbonate. *P ⬍
0.001 versus meal only; †P ⬍ 0.001 versus sevelamer carbonate. N ⫽ 18. ‡Containing 1,000 mg of elemental lanthanum.
**
Measured as phosphorus. Conversion factor for phosphorus in
milligrams to millimoles, ⫻0.0323.
Am J Kidney Dis. 2011;xx(x):xxx
of lanthanum carbonate and sevelamer carbonate.26,27
However, the colorimetric method for detection of
phosphorus30 used by Sheikh et al21 was not suitable
for quantification of phosphorus bound to lanthanum
because of the high affinity of lanthanum for phosphate, as shown previously in vitro.17 After further in
vitro investigation, an ICP-OES method that allowed
accurate assessment of phosphorus content of samples
was developed and validated.
Analysis of duplicates showed that the standardized
meal contained ⬃375 mg of phosphate, lower than
anticipated from reference data, but corresponding to
about one third of typical daily intake in the average
American diet in 2007.31 Consistent with the results
of Sheikh et al,21 ⬃75% of this phosphate was absorbed (net absorption, 281.7 ⫾ 14.1 mg from the
meal only; Fig 3). As expected, phosphate absorption
was decreased significantly by ingestion of a phosphate binder during the meal. A typical clinical dose
of lanthanum carbonate, containing 1,000 mg of elemental lanthanum, decreased phosphate absorption
by 45% (net absorption, 156.0 ⫾ 14.2 mg), and a
typical 2,400-mg dose of sevelamer carbonate decreased phosphate absorption by 21% (net absorption,
221.8 ⫾ 14.1 mg).
Calculation of phosphate-binding capacity showed
that a 1,000-mg dose of lanthanum (a single lantha-
Figure 4. Lanthanum carbonate binds significantly more
phosphate than sevelamer carbonate. *P ⬍ 0.001 versus
sevelamer carbonate. N ⫽ 18. †Containing 1,000 mg of elemental lanthanum. **Measured as phosphorus. Conversion factor for
phosphorus in milligrams to millimoles, ⫻0.0323.
5
Martin et al
num carbonate tablet) bound 135 mg of phosphate,
consistent with estimates of 79-156 mg calculated
using urinary phosphorus excretion in phase I studies.20 A 2,400-mg dose of sevelamer carbonate bound
63 mg of phosphate (equivalent to 21 mg of phosphate
per 800-mg tablet). Calculations based on urinary
phosphorus excretion suggest that sevelamer hydrochloride binds 18-29 mg of phosphate per 800-mg
tablet.19 The study by Sheikh et al21 indicated that a
dose of calcium acetate containing 1,000 mg of elemental calcium bound 177 mg of phosphate, equating to 30 mg of phosphate per 667-mg tablet.
This study used healthy volunteers because of the
extended study time and nature of the investigative
procedures. The study could have used patients with
CKD not yet on dialysis therapy, but phosphate absorption may not have remained constant during the times
involved because of the consequence of disease or its
treatment on vitamin D levels. Although phosphate
absorption may be slightly lower in patients with
CKD than in healthy people,32 this does not alter the
relative phosphate-binding capacities of the binders
under the conditions examined. Therefore, we would
not expect the choice of population to greatly influence
results. A limitation of this study was use of single doses
of the phosphate binders, rather than dosing to steady
state. However, this design along with the use of healthy
volunteers allowed indirect comparison with the historical results of Sheikh et al.21
The new KDIGO clinical practice guidelines recommend a decrease in serum phosphorus levels toward
the reference range in an attempt to decrease the high
mortality associated with increased serum phosphorus
levels in patients with CKD.4 Sustained control of
serum phosphorus levels to the target range of 3.5-5.5
mg/dL, previously recommended by KDOQI, is associated with a decrease in mortality risk in patients new
to dialysis therapy.3 Restriction of dietary phosphate
intake may be associated with protein malnutrition,
the risk of which may outweigh the benefit of controlled serum phosphorus levels and may even increase mortality.7 Increased protein intake with a
concurrent decrease in serum phosphorus levels has
been associated with lower mortality than decreases
in both parameters; efficacious phosphate binders,
particularly those that do not increase calcium load or
tablet burden, may be beneficial to decrease dietary
phosphorus absorption without protein restriction.7
The data presented here may be used with knowledge
of a patient’s dietary phosphate intake and dialysis
regimen to predict the decrease in phosphate load
achieved with the use of a phosphate binder. In the
future, this may allow better tailoring of phosphatebinder prescriptions to the individual patient’s needs.
A typical dose of lanthanum carbonate containing
6
1,000 mg of elemental lanthanum binds more than
twice as much phosphate as a typical 2,400-mg dose
of sevelamer carbonate. This translates into a lower
tablet number to achieve the same decrease in serum
phosphorus levels as sevelamer carbonate in clinical
practice.
In summary, lanthanum carbonate is an effective
noncalcium phosphate binder that binds significantly
more phosphate than sevelamer carbonate. Efficacious phosphate binders may help to achieve sustained control of serum phosphorus at the lower levels
suggested for patients with CKD by the new KDIGO
clinical practice guidelines, while allowing adequate
protein intake.
ACKNOWLEDGEMENTS
We thank Apinya Bee Vutikullird (West Coast Clinical Trials,
Cypress, CA), Heather Van Heusen (Shire Pharmaceuticals, Wayne,
PA), Michael Emmett (Baylor University Medical Center, Dallas,
TX), Peter Grohse (RTI Int, Research Triangle Park, NC), and Ping
Qiu (formerly of Shire Pharmaceuticals, Wayne, PA) for valuable
contributions to this study.
Support: Clinical research was funded by Shire Pharmaceuticals, which markets lanthanum carbonate. Paul Farrow, PhD, an
employee of Oxford PharmaGenesis Ltd, provided writing assistance to the authors. Editorial assistance in the form of proofreading, copy editing, and fact checking also was provided by Oxford
PharmaGenesis Ltd. These services were funded by Shire Pharmaceuticals. Patrick Martin, Phillip Wang, Antoine Robinson, Lynne
Poole, Jeffrey Dragone, and Michael Smyth are employees of
Shire Pharmaceuticals. Raymond Pratt was an employee of Shire
Pharmaceuticals at the time of the study and during manuscript
development.
Financial Disclosure: Aside from those reported in the previous
section, the authors declare that they have no relevant financial
interests.
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