Table 1.
Assessment of the safety pharmacology of lanthanum carbonate.
| Species | Study | Objective | Dose of lanthanum carbonate | Main findings |
|---|---|---|---|---|
| Cardiovascular system | ||||
| Dog | SPD/64/PH | Effects on cardiovascular function (anesthetized model) | 200, 600, or 2000 mg/kg (single dose, intraduodenal) | No effects of treatment on blood pressure (femoral artery), heart rate, left ventricular pressure, ECG waveform, or blood flow. |
| Dog | SPD0104 | Effects on cardiovascular function (4-week treatment) | 0.003, 0.05, or 1 mg/kg/day (28 days, intravenous chloride salt) | No treatment-related effects on ECG waveform. Doses gave plasma lanthanum Cmax values up to 20,000× those in humans (1 ng/mL). |
| Respiratory system | ||||
| Dog | SPD/64/PH | Effects on respiratory function (anesthetized model) | 200, 600, or 2000 mg/kg (single dose, intraduodenal) | No effects on respiration rate, tidal volume, or minute volume. |
| Central nervous system | ||||
| Rat | SPD/41/96 | Effects on neurobehavior | 2000 mg/kg (single, oral gavage) | Behavior unaffected and no overt signs of toxicity. |
| Mouse | SPD/42/96 | Effects on neurobehavior | 500, 1000, or 2000 mg/kg (single, oral gavage) | Behavior unaffected (with the exception of piloerection in two males, 4 h after administration of 2000 mg/kg) and there were no signs of toxicity. |
| Mouse | SPD/62/PH | Effects on body temperature and behavior | 200, 500, or 1000 mg/kg (single, oral gavage) | No effects on body temperature or pharmacological activity detectable by the Irwin test (all doses). |
| Mouse | SPD/63/PH | Effects on spontaneous motor activity | 200, 500, or 1000 mg/kg (single, oral gavage) | Line crossing values comparable with controls; no effect on spontaneous motor activity (all doses). |
| Mouse | SRU 003/992850 | Potential to induce proconvulsant activity | 500, 1000, or 2000 mg/kg (single, oral gavage) | No statistically significant proconvulsant activity in either the metrazol- or electroshock-induced tests, compared with the vehicle-treated control group. |
| Mouse | SRU 005/992851 | Potential to induce anticonvulsant activity | 500, 1000, or 2000 mg/kg (single, oral gavage) | No significant anticonvulsant activity in either the minimal metrazol or supramaximal electroshock test (all doses). |
| Dog | SPD/66/TK | Effects on neurobehavior, chronic treatment | 200, 600, or 2000 mg/kg/day (52-week treatment, oral capsule) | Assessment included anal sphincter tone, gait, patella reflex, panniculus reflex, pupillary response, ocular cephalic reflex, palpebral reflex, proprioception, righting reflex, withdrawal reflex. No treatment-related findings in the neurotoxicity assessment (all doses). |
| Mouse | SPD/88/C | Effects on neurobehavior, chronic treatment | 100 or 1500 mg/kg/day (62-week treatment, oral gavage) | No behavioral, autonomic, or neurologic effects (Irwin test, all doses). |
| Gastrointestinal tract | ||||
| Rat | SPD/47/PH | Effects on charcoal meal transit in the small intestine | 200, 500, or 1000 mg/kg (single, oral gavage) | 200, 500, or 1000 mg/kg (single, oral gavage) |
| Rat | SPD/49/PH | Effects on urinary and fecal output | 200, 500, or 1000 mg/kg (single, oral gavage) | No diarrhea or abnormal fecal output suggesting no disturbance of intestinal function. |
| Rat | SPD/48/PH | Effects on gastric acid secretion | 200, 500, or 1000 mg/kg (single, oral gavage) | No effect on volume of gastric acid secretion. Reduced acidity of gastric contents by neutralization at 1000 mg/kg. |
| Rat | SPD/50/PH | Potential to induce lesions in the stomach 200, 500, or 1000 mg/kg (single, oral gavage) | No gastric damage. | |
| Rat | SPD/51/PH | Effects on aspirin-induced gastric damage | 200, 500, or 1000 mg/kg (single, oral gavage) | No exacerbation of aspirin-induced gastric damage. |
Note: ECG, electrocardiogram.