Lipitor Clinical Pharmacology

Drug Library
Lipitor - Clinical Pharmacology [Atorvastatin]

Hypertriglyceridemia (Fredrickson Type IV)

The response to Lipitor in 64 patients with isolated hypertriglyceridemia treated across several clinical trials is shown in the table below. For the atorvastatin-treated patients, median (min, max) baseline TG level was 565 (267-1502).

TABLE 3. Combined Patients with Isolated Elevated TG:
Median (min, max) Percent Changes from Baseline
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Placebo
(N=12) Atorvastatin 10 mg
(N=37) Atorvastatin 20 mg
(N=13) Atorvastatin 80 mg
(N=14)
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Triglycerides -12 .4 (-36.6, 82.7) -41 .0 (-76.2, 49.4) -38 .7 (-62.7, 29.5) -51 .8 (-82.8, 41.3)
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Total-C -2 .3 (-15.5, 24.4) -28 .2 (-44.9, -6.8) -34 .9 (-49.6, -15.2) -44 .4 (-63.5, -3.8)
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LDL-C 3 .6 (-31.3, 31.6) -26 .5 (-57.7, 9.8) -30 .4 (-53.9, 0.3) -40 .5 (-60.6, -13.8)
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HDL-C 3 .8 (-18.6, 13.4) 13 .8 (-9.7, 61.5) 11 .0 (-3.2, 25.2) 7 .5 (-10.8, 37.2)
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VLDL-C -1 .0 (-31.9, 53.2) -48 .8 (-85.8, 57.3) -44 .6 (-62.2, -10.8) -62 .0 (-88.2, 37.6)
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non-HDL-C -2 .8 (-17.6, 30.0) -33 .0 (-52.1, -13.3) -42 .7 (-53.7, -17.4) -51 .5 (-72.9, -4.3)
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Dysbetalipoproteinemia (Fredrickson Type III)

The results of an open-label crossover study of 16 patients (genotypes: 14 apo E2/E2 and 2 apo E3/E2) with dysbetalipoproteinemia (Fredrickson Type III) are shown in the table below.

TABLE 4. Open-Label Crossover Study of 16 Patients
with Dysbetalipoproteinemia (Fredrickson Type III)
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Median % Change (min, max)
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Median (min, max) at Baseline (mg/dL) Atorvastatin 10 mg Atorvastatin 80 mg
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Total-C 442 (225, 1320) -37 (-85, 17) -58 (-90, -31)
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Triglycerides 678 (273, 5990) -39 (-92, -8) -53 (-95, -30)
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IDL-C + VLDL-C 215 (111, 613) -32 (-76, 9) -63 (-90, -8)
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non-HDL-C 411 (218, 1272) -43 (-87, -19) -64 (-92, -36)
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Homozygous Familial Hypercholesterolemia

In a study without a concurrent control group, 29 patients, ages 6 to 37 years with homozygous FH received maximum daily doses of 20 to 80 mg of Lipitor. The mean LDL-C reduction in this study was 18%. Twenty-five patients with a reduction in LDL-C had a mean response of 20% (range of 7% to 53%, median of 24%); the remaining 4 patients had 7% to 24% increases in LDL-C. Five of the 29 patients had absent LDL-receptor function. Of these, 2 patients also had a portacaval shunt and had no significant reduction in LDL-C. The remaining 3 receptor-negative patients had a mean LDL-C reduction of 22%.

Heterozygous Familial Hypercholesterolemia in Pediatric Patients

In a double-blind, placebo-controlled study followed by an open-label phase, 187 boys and postmenarchal girls 10-17 years of age (mean age 14.1 years) with heterozygous familial hypercholesterolemia (FH) or severe hypercholesterolemia were randomized to Lipitor (n=140) or placebo (n=47) for 26 weeks and then all received Lipitor for 26 weeks. Inclusion in the study required

1) a baseline LDL-C level 190 mg/dL or

2) a baseline LDL-C 160 mg/dL and positive family history of FH or documented premature cardiovascular disease in a first- or second-degree relative.

The mean baseline LDL-C value was 218.6 mg/dL (range: 138.5-385.0 mg/dL) in the Lipitor group compared to 230.0 mg/dL (range: 160.0-324.5 mg/dL) in the placebo group. The dosage of Lipitor (once daily) was 10 mg for the first 4 weeks and up-titrated to 20 mg if the LDLC level was > 130 mg/dL. The number of Lipitor-treated patients who required uptitration to 20 mg after week 4 during the double-blind phase was 80 (57.1%).

Lipitor significantly decreased plasma levels of total-C, LDL-C, triglycerides, and apolipoprotein B during the 26 week double-blind phase (see Table 5).

TABLE 5. Lipid-altering Effects of Lipitor in Adolescent Boys and Girls with Heterozygous Familial Hypercholesterolemia or Severe Hypercholesterolemia
(Mean Percent Change from Baseline at Endpoint in Intention-to-Treat Population)
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DOSAGE N Total-C LDL-C HDL-C TG Apolipoprotein B
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Placebo 47 -1.5 -0.4 -1.9 1.0 0.7

Lipitor 140 -31.4 -39.6 2.8 -12.0 -34.0
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The mean achieved LDL-C value was 130.7 mg/dL (range: 70.0-242.0 mg/dL) in the Lipitor group compared to 228.5 mg/dL (range: 152.0-385.0 mg/dL) in the placebo group during the 26 week double-blind phase.

The safety and efficacy of doses above 20 mg have not been studied in controlled trials in children. The long-term efficacy of Lipitor therapy in childhood to reduce morbidity and mortality in adulthood has not been established.