BIOAVAILABILITY (F)
- Intramuscular: poor
- Ophthalmic: none
-Oral, oral solution Sandimmune®: 10% to 89%.
- Neoral® 23% higher than the conventional cyclosporine.
- Rectal, water or oil retention enema: Minimal
- Ophthalmic: none
-Oral, oral solution Sandimmune®: 10% to 89%.
- Neoral® 23% higher than the conventional cyclosporine.
- Rectal, water or oil retention enema: Minimal
ABSORPTION
-Absorption of cyclosporine is primarily in the duodenum and the jejunum
- Absorption of cyclosporine exhibits large intra- and inter-patient variability
- Absorption of cyclosporine is decreased sharply by mild diarrhea
- Other factors which influence absorption include intestinal disease, intestinal surgery, or bowel length.
- The fraction of cyclosporine absorbed is lower in black patients (30.9%) compared to white patients (39.5%).
-Concomitant administration of cyclosporine and d-alpha-tocopheryl poly ethylene glycol-1000 (TPGS) significantly increased the bioavailability of oral cyclosporine in children
-After liver transplantation, bile production and flow may not begin immediately.
-In the absence of bile salts, the absorption of cyclosporine can be greatly decreased. Bile appears to assist in the dissolution of cyclosporine which increases the absorption of the drug.
- Absorption of cyclosporine exhibits large intra- and inter-patient variability
- Absorption of cyclosporine is decreased sharply by mild diarrhea
- Other factors which influence absorption include intestinal disease, intestinal surgery, or bowel length.
- The fraction of cyclosporine absorbed is lower in black patients (30.9%) compared to white patients (39.5%).
-Concomitant administration of cyclosporine and d-alpha-tocopheryl poly ethylene glycol-1000 (TPGS) significantly increased the bioavailability of oral cyclosporine in children
-After liver transplantation, bile production and flow may not begin immediately.
-In the absence of bile salts, the absorption of cyclosporine can be greatly decreased. Bile appears to assist in the dissolution of cyclosporine which increases the absorption of the drug.
EFFECTS OF FOOD.
-Food containing a large amount of fat enhances the absorption of cyclosporine.
-Oral cyclosporine solution is prepared with olive oil and alcohol to enhance the solubility of the drug
- The solution is mixed in milk, chocolate milk, or orange juice using a glass container immediately before swallowing.
-Oral cyclosporine solution is prepared with olive oil and alcohol to enhance the solubility of the drug
- The solution is mixed in milk, chocolate milk, or orange juice using a glass container immediately before swallowing.
DISTRIBUTION SITES
-TOTAL PROTEIN BINDING: 90%
-Cyclosporine is bound primarily to lipoproteins
- 33% to 47% in plasma, 4% to 9% in lymphocytes, 5% to 12% in granulocytes, and 41% to 58% in erythrocytes
- Fat, extensive
-Kidney, extensive.
-Liver, extensive.
- Pancreas, extensive.
-Skin, 10% (blister fluid).
- Synovial fluid, 31%.
-Cyclosporine is bound primarily to lipoproteins
- 33% to 47% in plasma, 4% to 9% in lymphocytes, 5% to 12% in granulocytes, and 41% to 58% in erythrocytes
- Fat, extensive
-Kidney, extensive.
-Liver, extensive.
- Pancreas, extensive.
-Skin, 10% (blister fluid).
- Synovial fluid, 31%.
DISTRIBUTION KINETICS.
- Volume of Distribution (Vd): 3 to 5 L/kg
- 4.5 L/kg for renal transplant patients
- 3.9 L/kg during liver disease.
- 0.9 L/kg for children with cardiac failure.
- In bone marrow transplant patients, the Vd for cyclosporine changes over 3 weeks.
- the mean volume of distribution was 27.2 L, in 3 weeks.
- The volume of distribution decreased to 21.8 L
- 4.5 L/kg for renal transplant patients
- 3.9 L/kg during liver disease.
- 0.9 L/kg for children with cardiac failure.
- In bone marrow transplant patients, the Vd for cyclosporine changes over 3 weeks.
- the mean volume of distribution was 27.2 L, in 3 weeks.
- The volume of distribution decreased to 21.8 L
METABOLISM
- Intestinal wall, small
- Kidney, small
- Liver, extensive
- Cyclosporine is metabolized by the cytochrome P-450 III-A 4 enzyme.
- Kidney, small
- Liver, extensive
- Cyclosporine is metabolized by the cytochrome P-450 III-A 4 enzyme.
EXCRETION
- BREASTFEEDING: Unsafe
- RENAL EXCRETION: 6%
-Only 0.1% of a cyclosporine dose is eliminated in the urine as unchanged drug; the remainder is eliminated as metabolites.
-Bile, Extensive
- RENAL EXCRETION: 6%
-Only 0.1% of a cyclosporine dose is eliminated in the urine as unchanged drug; the remainder is eliminated as metabolites.
-Bile, Extensive
HALF-LIFE.
-HALF-LIFE: 8 hours (range 5 to 18 hours)
MONITORING PARAMETERS.
I- THERAPEUTIC:
-LABORATORY PARAMETERS
-Patients are usually monitored by their cyclosporine trough conc., area-underthe- curve (AUC), or a sparse-sample method (drug conc. at few time points).
-Organ biopsy for signs of rejection.
-Lymphokine levels.
-Soluble interleukin-2 receptor levels
-Physical Examination.
-Decreased signs of inflammation in autoimmune disease.
II- TOXIC.
-LABORATORY PARAMETERS.
-Renal function tests
-Rheumatoid arthritis, serum Creatinine should be monitored every 2 weeks for the first 3 months and if stable, monthly there after.
-When dosage adjustments are made or the serum creatinine increases, more frequent monitoring is recommended.
-Psoriasis, serum creatinine should be monitored every 2 weeks for the first 6 weeks and if stable, monthly there after.
-When dosage adjustments are made or the serum creatinine increases, more frequent monitoring is recommended.
-If serum creatinine increases by > 30% above baseline (measured on 2 different days), the dose of cyclosporine should be decreased by 0.5 to 1 mg/kg.
-If the serum creatinine decreases to less than 30%, cyclosporine may be continued.
-if the serum creatinine remains elevated, cyclosporine should be stopped within 1 month. -Cyclosporine may be resumed if the serum creatinine returns to less than 10% (psoriasis) or 15% (rheumatoid arthritis) of baseline.
-Cholesterol and lipoprotein levels
-Serum electrolytes
-Physical examination.
-Signs and symptoms of infection
-Signs of gastrointestinal distress
-Hypertrichosis
-Headache
MONITORING PARAMETERS.
I- THERAPEUTIC:
-LABORATORY PARAMETERS
-Patients are usually monitored by their cyclosporine trough conc., area-underthe- curve (AUC), or a sparse-sample method (drug conc. at few time points).
-Organ biopsy for signs of rejection.
-Lymphokine levels.
-Soluble interleukin-2 receptor levels
-Physical Examination.
-Decreased signs of inflammation in autoimmune disease.
II- TOXIC.
-LABORATORY PARAMETERS.
-Renal function tests
-Rheumatoid arthritis, serum Creatinine should be monitored every 2 weeks for the first 3 months and if stable, monthly there after.
-When dosage adjustments are made or the serum creatinine increases, more frequent monitoring is recommended.
-Psoriasis, serum creatinine should be monitored every 2 weeks for the first 6 weeks and if stable, monthly there after.
-When dosage adjustments are made or the serum creatinine increases, more frequent monitoring is recommended.
-If serum creatinine increases by > 30% above baseline (measured on 2 different days), the dose of cyclosporine should be decreased by 0.5 to 1 mg/kg.
-If the serum creatinine decreases to less than 30%, cyclosporine may be continued.
-if the serum creatinine remains elevated, cyclosporine should be stopped within 1 month. -Cyclosporine may be resumed if the serum creatinine returns to less than 10% (psoriasis) or 15% (rheumatoid arthritis) of baseline.
-Cholesterol and lipoprotein levels
-Serum electrolytes
-Physical examination.
-Signs and symptoms of infection
-Signs of gastrointestinal distress
-Hypertrichosis
-Headache
-Blood pressure
-For patients with rheumatoid arthritis, blood pressure should be monitored every 2 weeks for the first 3 months and if stable, monthly there after.
-For patients with psoriasis, blood pressure should be monitored every 2 weeks for the first 6 weeks and if stable, monthly thereafter.
-For patients with psoriasis, blood pressure should be monitored every 2 weeks for the first 6 weeks and if stable, monthly thereafter.