Pharmacokinetic-pharmacodynamic crossover comparison of two levodopa extension strategies
Controlled‐release carbidopa and levodopa (CL‐CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa (L‐dopa) effects. In a randomized, open‐label crossover study of 17 PD subjects with wearing‐off responses, we compared 8‐hour L‐dopa pharmacokinetics (P...
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| Published in | Movement disorders Vol. 24; no. 9; pp. 1319 - 1324 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
15.07.2009
Wiley |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0885-3185 1531-8257 1531-8257 |
| DOI | 10.1002/mds.22587 |
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| Abstract | Controlled‐release carbidopa and levodopa (CL‐CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa (L‐dopa) effects. In a randomized, open‐label crossover study of 17 PD subjects with wearing‐off responses, we compared 8‐hour L‐dopa pharmacokinetics (PK) and clinical effects after two doses of CL‐CR (50 and 200 mg, respectively) and CLE (37.7, 150, 200 mg, respectively). PK analysis revealed the anticipated near‐equivalent mean L‐dopa area‐under‐the‐concentration‐curve values (639,490 ng min/mL for two doses of CLE, and 662,577 for CL‐CR, P = 0.86). The mean hourly fluctuation index for L‐dopa concentration was 235% for CLE and 196% for CL‐CR (P = 0.004). The mean maximal concentration for the first CLE dose was 1,926 ± 760 ng/mL and for CL‐CR, 1,840 ± 889 (P = 0.33). During the PK studies, the mean time that L‐dopa concentration was ≥1,000 ng/mL for CLE was 291 ± 88 minutes and for CL‐CR, 306 ± 86 (P = 0.33). The mean percent‐time in “off” state was 18% for CLE and 28% for CL‐CR (P = 0.017), “on state without dyskinesia” was 64% for CLE and 65% for CL‐CR (P = 0.803), and “on state with nontroublesome dyskinesia” was 18% for CLE and 7% for CL‐CR (P = 0.03). Despite less “off” time with CLE, both formulations demonstrated similar mean PK values and marked intersubject PK variability. © 2009 Movement Disorder Society |
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| AbstractList | Controlled-release carbidopa and levodopa (CL-CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa (L-dopa) effects. In a randomized, open-label crossover study of 17 PD subjects with wearing-off responses, we compared 8-hour L-dopa pharmacokinetics (PK) and clinical effects after two doses of CL-CR (50 and 200 mg, respectively) and CLE (37.7, 150, 200 mg, respectively). PK analysis revealed the anticipated near-equivalent mean L-dopa area-under-the-concentration-curve values (639,490 ng min/mL for two doses of CLE, and 662,577 for CL-CR, P = 0.86). The mean hourly fluctuation index for L-dopa concentration was 235% for CLE and 196% for CL-CR (P = 0.004). The mean maximal concentration for the first CLE dose was 1,926 ± 760 ng/mL and for CL-CR, 1,840 ± 889 (P = 0.33). During the PK studies, the mean time that L-dopa concentration was 1,000 ng/mL for CLE was 291 ± 88 minutes and for CL-CR, 306 ± 86 (P = 0.33). The mean percent-time in off state was 18% for CLE and 28% for CL-CR (P = 0.017), on state without dyskinesia was 64% for CLE and 65% for CL-CR (P = 0.803), and on state with nontroublesome dyskinesia was 18% for CLE and 7% for CL-CR (P = 0.03). Despite less off time with CLE, both formulations demonstrated similar mean PK values and marked intersubject PK variability. Controlled‐release carbidopa and levodopa (CL‐CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa ( L ‐dopa) effects. In a randomized, open‐label crossover study of 17 PD subjects with wearing‐off responses, we compared 8‐hour L ‐dopa pharmacokinetics (PK) and clinical effects after two doses of CL‐CR (50 and 200 mg, respectively) and CLE (37.7, 150, 200 mg, respectively). PK analysis revealed the anticipated near‐equivalent mean L ‐dopa area‐under‐the‐concentration‐curve values (639,490 ng min/mL for two doses of CLE, and 662,577 for CL‐CR, P = 0.86). The mean hourly fluctuation index for L ‐dopa concentration was 235% for CLE and 196% for CL‐CR ( P = 0.004). The mean maximal concentration for the first CLE dose was 1,926 ± 760 ng/mL and for CL‐CR, 1,840 ± 889 ( P = 0.33). During the PK studies, the mean time that L ‐dopa concentration was ≥1,000 ng/mL for CLE was 291 ± 88 minutes and for CL‐CR, 306 ± 86 ( P = 0.33). The mean percent‐time in “ off ” state was 18% for CLE and 28% for CL‐CR ( P = 0.017), “ on state without dyskinesia ” was 64% for CLE and 65% for CL‐CR ( P = 0.803), and “ on state with nontroublesome dyskinesia ” was 18% for CLE and 7% for CL‐CR ( P = 0.03). Despite less “ off ” time with CLE, both formulations demonstrated similar mean PK values and marked intersubject PK variability. © 2009 Movement Disorder Society Controlled‐release carbidopa and levodopa (CL‐CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa (L‐dopa) effects. In a randomized, open‐label crossover study of 17 PD subjects with wearing‐off responses, we compared 8‐hour L‐dopa pharmacokinetics (PK) and clinical effects after two doses of CL‐CR (50 and 200 mg, respectively) and CLE (37.7, 150, 200 mg, respectively). PK analysis revealed the anticipated near‐equivalent mean L‐dopa area‐under‐the‐concentration‐curve values (639,490 ng min/mL for two doses of CLE, and 662,577 for CL‐CR, P = 0.86). The mean hourly fluctuation index for L‐dopa concentration was 235% for CLE and 196% for CL‐CR (P = 0.004). The mean maximal concentration for the first CLE dose was 1,926 ± 760 ng/mL and for CL‐CR, 1,840 ± 889 (P = 0.33). During the PK studies, the mean time that L‐dopa concentration was ≥1,000 ng/mL for CLE was 291 ± 88 minutes and for CL‐CR, 306 ± 86 (P = 0.33). The mean percent‐time in “off” state was 18% for CLE and 28% for CL‐CR (P = 0.017), “on state without dyskinesia” was 64% for CLE and 65% for CL‐CR (P = 0.803), and “on state with nontroublesome dyskinesia” was 18% for CLE and 7% for CL‐CR (P = 0.03). Despite less “off” time with CLE, both formulations demonstrated similar mean PK values and marked intersubject PK variability. © 2009 Movement Disorder Society Controlled-release carbidopa and levodopa (CL-CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa (L-dopa) effects. In a randomized, open-label crossover study of 17 PD subjects with wearing-off responses, we compared 8-hour L-dopa pharmacokinetics (PK) and clinical effects after two doses of CL-CR (50 and 200 mg, respectively) and CLE (37.7, 150, 200 mg, respectively). PK analysis revealed the anticipated near-equivalent mean L-dopa area-under-the-concentration-curve values (639,490 ng min/mL for two doses of CLE, and 662,577 for CL-CR, P = 0.86). The mean hourly fluctuation index for L-dopa concentration was 235% for CLE and 196% for CL-CR (P = 0.004). The mean maximal concentration for the first CLE dose was 1,926 +/- 760 ng/mL and for CL-CR, 1,840 +/- 889 (P = 0.33). During the PK studies, the mean time that L-dopa concentration was > or =1,000 ng/mL for CLE was 291 +/- 88 minutes and for CL-CR, 306 +/- 86 (P = 0.33). The mean percent-time in "off" state was 18% for CLE and 28% for CL-CR (P = 0.017), "on state without dyskinesia" was 64% for CLE and 65% for CL-CR (P = 0.803), and "on state with nontroublesome dyskinesia" was 18% for CLE and 7% for CL-CR (P = 0.03). Despite less "off" time with CLE, both formulations demonstrated similar mean PK values and marked intersubject PK variability. Controlled-release carbidopa and levodopa (CL-CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa (L-dopa) effects. In a randomized, open-label crossover study of 17 PD subjects with wearing-off responses, we compared 8-hour L-dopa pharmacokinetics (PK) and clinical effects after two doses of CL-CR (50 and 200 mg, respectively) and CLE (37.7, 150, 200 mg, respectively). PK analysis revealed the anticipated near-equivalent mean L-dopa area-under-the-concentration-curve values (639,490 ng min/mL for two doses of CLE, and 662,577 for CL-CR, P = 0.86). The mean hourly fluctuation index for L-dopa concentration was 235% for CLE and 196% for CL-CR (P = 0.004). The mean maximal concentration for the first CLE dose was 1,926 +/- 760 ng/mL and for CL-CR, 1,840 +/- 889 (P = 0.33). During the PK studies, the mean time that L-dopa concentration was > or =1,000 ng/mL for CLE was 291 +/- 88 minutes and for CL-CR, 306 +/- 86 (P = 0.33). The mean percent-time in "off" state was 18% for CLE and 28% for CL-CR (P = 0.017), "on state without dyskinesia" was 64% for CLE and 65% for CL-CR (P = 0.803), and "on state with nontroublesome dyskinesia" was 18% for CLE and 7% for CL-CR (P = 0.03). Despite less "off" time with CLE, both formulations demonstrated similar mean PK values and marked intersubject PK variability.Controlled-release carbidopa and levodopa (CL-CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa (L-dopa) effects. In a randomized, open-label crossover study of 17 PD subjects with wearing-off responses, we compared 8-hour L-dopa pharmacokinetics (PK) and clinical effects after two doses of CL-CR (50 and 200 mg, respectively) and CLE (37.7, 150, 200 mg, respectively). PK analysis revealed the anticipated near-equivalent mean L-dopa area-under-the-concentration-curve values (639,490 ng min/mL for two doses of CLE, and 662,577 for CL-CR, P = 0.86). The mean hourly fluctuation index for L-dopa concentration was 235% for CLE and 196% for CL-CR (P = 0.004). The mean maximal concentration for the first CLE dose was 1,926 +/- 760 ng/mL and for CL-CR, 1,840 +/- 889 (P = 0.33). During the PK studies, the mean time that L-dopa concentration was > or =1,000 ng/mL for CLE was 291 +/- 88 minutes and for CL-CR, 306 +/- 86 (P = 0.33). The mean percent-time in "off" state was 18% for CLE and 28% for CL-CR (P = 0.017), "on state without dyskinesia" was 64% for CLE and 65% for CL-CR (P = 0.803), and "on state with nontroublesome dyskinesia" was 18% for CLE and 7% for CL-CR (P = 0.03). Despite less "off" time with CLE, both formulations demonstrated similar mean PK values and marked intersubject PK variability. |
| Author | Jennings, Danna Rabinowicz, Adrian L. LeWitt, Peter A. Murck, Harold Wang, James Hubble, Jean P. Guarnieri, Maria Pahwa, Rajesh Lyons, Kelly E. |
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| Keywords | Fluctuations Nervous system diseases Pharmacodynamics Parkinson's disease motor fluctuation Parkinson disease Cerebral disorder Central nervous system disease Entacapone Strategy Degenerative disease Levodopa Pharmacokinetics Comparative study Extrapyramidal syndrome |
| Language | English |
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| Notes | ark:/67375/WNG-MFJ161MH-D Potential conflict of interest: Drs. LeWitt, Jennings, Lyons, and Pahwa: received contractual payments from Novartis Pharmaceutical Corporation for the conduct of this study through their respective institutions, and each have also received compensation for other activities with Novartis, including scientific advisory roles, sponsored clinical trials, and lectures; Dr. Rabinowicz: a former employee of Novartis Pharmaceutical Corporation, is currently with Bayer HealthCare Pharmaceuticals, Wayne, NY; Dr. Hubble: a former employee of Novartis Pharmaceutical Corporation, is currently with Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT; Drs. Guarnieri and Wang: are employees of Novartis Pharmaceutical Corporation; Dr. Murck: is a former employee of Novartis Pharmaceutical Corporation, and is currently with Bristol-Myers Squibb Company, Plainsboro, NJ. ArticleID:MDS22587 istex:CE60AC3975D087FFD56D71501497A712CEAED1D8 Potential conflict of interest: Drs. LeWitt, Jennings, Lyons, and Pahwa: received contractual payments from Novartis Pharmaceutical Corporation for the conduct of this study through their respective institutions, and each have also received compensation for other activities with Novartis, including scientific advisory roles, sponsored clinical trials, and lectures; Dr. Rabinowicz: a former employee of Novartis Pharmaceutical Corporation, is currently with Bayer HealthCare Pharmaceuticals, Wayne, NY; Dr. Hubble: a former employee of Novartis Pharmaceutical Corporation, is currently with Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT; Drs. Guarnieri and Wang: are employees of Novartis Pharmaceutical Corporation; Dr. Murck: is a former employee of Novartis Pharmaceutical Corporation, and is currently with Bristol‐Myers Squibb Company, Plainsboro, NJ. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 ObjectType-Undefined-3 |
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| References | Hauser RA,Friedlander J,Zesiewicz TA, et al. A home diary to assess functional status in patients with Parkinson's disease with motor fluctuations and dyskinesia. Clin Neuropharmacol 2000; 23: 75-81. Chan PL,Nutt JG,Holford NH. Pharmacokinetic and pharmacodynamic changes during the first four years of levodopa treatment in Parkinson's disease. J Pharmacokinet Pharmacodyn 2005; 32: 459-484. Müller T,Ander L,Kolf K,Woitalla D,Muhlack S. Comparison of 200 mg retarded release levodopa/carbidopa-with 150 mg levodopa/carbidopa/entacapone application: pharmacokinetics and efficacy in patients with Parkinson's disease. J Neural Transm 2007; 114: 1457-1462. Doller HJ,Connor JD. Changes in neostriatal dopamine concentrations in response to levodopa infusions. J Neurochem 1980; 34: 1264-1269. Müller T,Erdmann C,Muhlack S, et al. Pharmacokinetic behavior of levodopa and 3-O-methyldopa after repeat administration of levodopa/carbidopa with and without entacapone in patients with Parkinson's disease. J Neural Transm 2006; 113: 1441-1448. Ahtila S,Kaakkola S,Gordin A, et al. Effect of entacapone, a COMT inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of controlled-release levodopa-carbidopa in volunteers. Clin Neuropharmacol 1995; 18: 46-57. Cedarbaum JM,Hoey M,McDowell FH. A double-blind crossover comparison of Sinemet CR4 and standard Sinemet 25/100 in patients with Parkinson's disease and fluctuating motor performance. J Neurol Neurosurg Psychiatry 1989; 52: 207-212. Piccini P,Brooks DJ,Korpela K, et al. The catechol-O-methyltransferase (COMT) inhibitor entacapone enhances the pharmacokinetic and clinical response to Sinemet CR in Parkinson's disease. J Neurol Neurosurg Psychiatry 2000; 68: 589-594. Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson's disease in DATATOP subjects requiring levodopa. Ann Neurol 1996; 39: 37-45. Merello M,Lees AJ,Webster R, et al. Effect of entacapone, a peripherally acting catechol-O-methyltransferase inhibitor, on the motor response to acute treatment with levodopa in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry 1994; 57: 186-189. Hoehn MM,Yahr MD. Parkinsonism: onset, progression, and mortality. Neurology 1967; 17: 427-442. Paija O,Laine K,Kultalahti ER, et al. Entacapone increases levodopa exposure and reduces plasma levodopa variability when used with Sinemet CR. Clin Neuropharmacol 2005; 28: 115-119. LeWitt PA,Nelson MV,Berchou RC, et al. Controlled-release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies. Neurology 1989; 39( suppl 2): 45-53. Zappia M,Bosco D,Plastino M, et al. Pharmacodynamics of the long-duration response to levodopa in PD. Neurology 1999; 53: 557-560. Koller WC. Alternate day levodopa therapy in Parkinsonism. Neurology 1982; 32: 324-326. Nelson MV,Berchou RC,LeWitt PA, et al. Pharmacodynamic modeling of concentration-effect relationships after controlled-release carbidopa/levodopa (Sinemet CR4) in Parkinson's disease. Neurology 1990; 40: 70-74. Heikkinen H,Nutt JG,LeWitt PA, et al. The effects of different repeated doses of entacapone on the pharmacokinetics of L-Dopa and on the clinical response to L-Dopa in Parkinson's disease. Clin Neuropharmacol 2001; 24: 150-157. 1990; 40 2007; 114 1989; 52 1987; 2 1989; 88 1996; 39 2000; 23 2000; 68 1980; 34 1982; 32 1967; 17 2005; 32 1994; 57 1999; 53 1995; 18 2001; 24 2005; 28 1989; 39 2006; 113 e_1_2_7_5_2 e_1_2_7_4_2 LeWitt P (e_1_2_7_2_2) 1989 e_1_2_7_3_2 e_1_2_7_9_2 e_1_2_7_7_2 e_1_2_7_6_2 e_1_2_7_19_2 e_1_2_7_18_2 e_1_2_7_17_2 e_1_2_7_16_2 e_1_2_7_15_2 e_1_2_7_14_2 e_1_2_7_13_2 e_1_2_7_12_2 e_1_2_7_10_2 e_1_2_7_20_2 Fahn S (e_1_2_7_11_2) 1987 LeWitt PA (e_1_2_7_8_2) 1989; 39 |
| References_xml | – reference: Koller WC. Alternate day levodopa therapy in Parkinsonism. Neurology 1982; 32: 324-326. – reference: Chan PL,Nutt JG,Holford NH. Pharmacokinetic and pharmacodynamic changes during the first four years of levodopa treatment in Parkinson's disease. J Pharmacokinet Pharmacodyn 2005; 32: 459-484. – reference: LeWitt PA,Nelson MV,Berchou RC, et al. Controlled-release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies. Neurology 1989; 39( suppl 2): 45-53. – reference: Piccini P,Brooks DJ,Korpela K, et al. The catechol-O-methyltransferase (COMT) inhibitor entacapone enhances the pharmacokinetic and clinical response to Sinemet CR in Parkinson's disease. J Neurol Neurosurg Psychiatry 2000; 68: 589-594. – reference: Heikkinen H,Nutt JG,LeWitt PA, et al. The effects of different repeated doses of entacapone on the pharmacokinetics of L-Dopa and on the clinical response to L-Dopa in Parkinson's disease. Clin Neuropharmacol 2001; 24: 150-157. – reference: Müller T,Ander L,Kolf K,Woitalla D,Muhlack S. Comparison of 200 mg retarded release levodopa/carbidopa-with 150 mg levodopa/carbidopa/entacapone application: pharmacokinetics and efficacy in patients with Parkinson's disease. J Neural Transm 2007; 114: 1457-1462. – reference: Paija O,Laine K,Kultalahti ER, et al. Entacapone increases levodopa exposure and reduces plasma levodopa variability when used with Sinemet CR. Clin Neuropharmacol 2005; 28: 115-119. – reference: Doller HJ,Connor JD. Changes in neostriatal dopamine concentrations in response to levodopa infusions. J Neurochem 1980; 34: 1264-1269. – reference: Nelson MV,Berchou RC,LeWitt PA, et al. Pharmacodynamic modeling of concentration-effect relationships after controlled-release carbidopa/levodopa (Sinemet CR4) in Parkinson's disease. Neurology 1990; 40: 70-74. – reference: Hoehn MM,Yahr MD. Parkinsonism: onset, progression, and mortality. Neurology 1967; 17: 427-442. – reference: Ahtila S,Kaakkola S,Gordin A, et al. Effect of entacapone, a COMT inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of controlled-release levodopa-carbidopa in volunteers. Clin Neuropharmacol 1995; 18: 46-57. – reference: Müller T,Erdmann C,Muhlack S, et al. Pharmacokinetic behavior of levodopa and 3-O-methyldopa after repeat administration of levodopa/carbidopa with and without entacapone in patients with Parkinson's disease. J Neural Transm 2006; 113: 1441-1448. – reference: Zappia M,Bosco D,Plastino M, et al. Pharmacodynamics of the long-duration response to levodopa in PD. Neurology 1999; 53: 557-560. – reference: Cedarbaum JM,Hoey M,McDowell FH. A double-blind crossover comparison of Sinemet CR4 and standard Sinemet 25/100 in patients with Parkinson's disease and fluctuating motor performance. J Neurol Neurosurg Psychiatry 1989; 52: 207-212. – reference: Merello M,Lees AJ,Webster R, et al. Effect of entacapone, a peripherally acting catechol-O-methyltransferase inhibitor, on the motor response to acute treatment with levodopa in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry 1994; 57: 186-189. – reference: Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson's disease in DATATOP subjects requiring levodopa. Ann Neurol 1996; 39: 37-45. – reference: Hauser RA,Friedlander J,Zesiewicz TA, et al. A home diary to assess functional status in patients with Parkinson's disease with motor fluctuations and dyskinesia. Clin Neuropharmacol 2000; 23: 75-81. – volume: 53 start-page: 557 year: 1999 end-page: 560 article-title: Pharmacodynamics of the long‐duration response to levodopa in PD publication-title: Neurology – volume: 52 start-page: 207 year: 1989 end-page: 212 article-title: A double‐blind crossover comparison of Sinemet CR4 and standard Sinemet 25/100 in patients with Parkinson's disease and fluctuating motor performance publication-title: J Neurol Neurosurg Psychiatry – volume: 40 start-page: 70 year: 1990 end-page: 74 article-title: Pharmacodynamic modeling of concentration‐effect relationships after controlled‐release carbidopa/levodopa (Sinemet CR4) in Parkinson's disease publication-title: Neurology – volume: 114 start-page: 1457 year: 2007 end-page: 1462 article-title: Comparison of 200 mg retarded release levodopa/carbidopa—with 150 mg levodopa/carbidopa/entacapone application: pharmacokinetics and efficacy in patients with Parkinson's disease publication-title: J Neural Transm – volume: 24 start-page: 150 year: 2001 end-page: 157 article-title: The effects of different repeated doses of entacapone on the pharmacokinetics of L‐Dopa and on the clinical response to L‐Dopa in Parkinson's disease publication-title: Clin Neuropharmacol – volume: 32 start-page: 324 year: 1982 end-page: 326 article-title: Alternate day levodopa therapy in Parkinsonism publication-title: Neurology – volume: 68 start-page: 589 year: 2000 end-page: 594 article-title: The catechol‐O‐methyltransferase (COMT) inhibitor entacapone enhances the pharmacokinetic and clinical response to Sinemet CR in Parkinson's disease publication-title: J Neurol Neurosurg Psychiatry – volume: 39 start-page: 45 issue: suppl 2 year: 1989 end-page: 53 article-title: Controlled‐release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies publication-title: Neurology – volume: 18 start-page: 46 year: 1995 end-page: 57 article-title: Effect of entacapone, a COMT inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of controlled‐release levodopa‐carbidopa in volunteers publication-title: Clin Neuropharmacol – volume: 57 start-page: 186 year: 1994 end-page: 189 article-title: Effect of entacapone, a peripherally acting catechol‐O‐methyltransferase inhibitor, on the motor response to acute treatment with levodopa in patients with Parkinson's disease publication-title: J Neurol Neurosurg Psychiatry – volume: 32 start-page: 459 year: 2005 end-page: 484 article-title: Pharmacokinetic and pharmacodynamic changes during the first four years of levodopa treatment in Parkinson's disease publication-title: J Pharmacokinet Pharmacodyn – volume: 17 start-page: 427 year: 1967 end-page: 442 article-title: Parkinsonism: onset, progression, and mortality publication-title: Neurology – volume: 88 start-page: 325 year: 1989 end-page: 384 – volume: 39 start-page: 37 year: 1996 end-page: 45 article-title: Impact of deprenyl and tocopherol treatment on Parkinson's disease in DATATOP subjects requiring levodopa publication-title: Ann Neurol – volume: 34 start-page: 1264 year: 1980 end-page: 1269 article-title: Changes in neostriatal dopamine concentrations in response to levodopa infusions publication-title: J Neurochem – volume: 2 start-page: 153 year: 1987 end-page: 163 – volume: 113 start-page: 1441 year: 2006 end-page: 1448 article-title: Pharmacokinetic behavior of levodopa and 3‐O‐methyldopa after repeat administration of levodopa/carbidopa with and without entacapone in patients with Parkinson's disease publication-title: J Neural Transm – volume: 28 start-page: 115 year: 2005 end-page: 119 article-title: Entacapone increases levodopa exposure and reduces plasma levodopa variability when used with Sinemet CR publication-title: Clin Neuropharmacol – volume: 23 start-page: 75 year: 2000 end-page: 81 article-title: A home diary to assess functional status in patients with Parkinson's disease with motor fluctuations and dyskinesia publication-title: Clin Neuropharmacol – ident: e_1_2_7_13_2 doi: 10.1212/WNL.40.1.70 – ident: e_1_2_7_9_2 doi: 10.1136/jnnp.52.2.207 – ident: e_1_2_7_10_2 doi: 10.1097/00002826-200105000-00006 – ident: e_1_2_7_12_2 doi: 10.1097/00002826-200003000-00003 – ident: e_1_2_7_6_2 doi: 10.1111/j.1471-4159.1980.tb09969.x – ident: e_1_2_7_14_2 doi: 10.1097/00002826-199502000-00006 – ident: e_1_2_7_5_2 doi: 10.1007/s10928-005-0055-x – ident: e_1_2_7_3_2 doi: 10.1212/WNL.32.3.324 – ident: e_1_2_7_15_2 doi: 10.1007/s00702-006-0442-5 – start-page: 153 year: 1987 ident: e_1_2_7_11_2 – ident: e_1_2_7_16_2 doi: 10.1136/jnnp.57.2.186 – ident: e_1_2_7_17_2 doi: 10.1097/01.wnf.0000166393.33781.87 – ident: e_1_2_7_20_2 doi: 10.1212/WNL.17.5.427 – volume: 39 start-page: 45 issue: 2 year: 1989 ident: e_1_2_7_8_2 article-title: Controlled‐release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies publication-title: Neurology – ident: e_1_2_7_7_2 doi: 10.1212/WNL.53.3.557 – ident: e_1_2_7_19_2 doi: 10.1007/s00702-007-0773-x – start-page: 325 volume-title: Handbook of experimental pharmacology year: 1989 ident: e_1_2_7_2_2 – ident: e_1_2_7_4_2 doi: 10.1002/ana.410390107 – ident: e_1_2_7_18_2 doi: 10.1136/jnnp.68.5.589 |
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| Snippet | Controlled‐release carbidopa and levodopa (CL‐CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa (L‐dopa)... Controlled‐release carbidopa and levodopa (CL‐CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa ( L ‐dopa)... Controlled-release carbidopa and levodopa (CL-CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa (L-dopa)... |
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| SubjectTerms | Aged Analysis of Variance Antiparkinson Agents - blood Antiparkinson Agents - pharmacokinetics Antiparkinson Agents - therapeutic use Biological and medical sciences Carbidopa - pharmacokinetics Carbidopa - therapeutic use Catechols - pharmacokinetics Catechols - therapeutic use Cross-Over Studies Disability Evaluation Dose-Response Relationship, Drug Drug Delivery Systems - classification Drug Delivery Systems - methods Drug Therapy, Combination Drug toxicity and drugs side effects treatment entacapone Female Humans levodopa Levodopa - blood Levodopa - pharmacokinetics Levodopa - therapeutic use Male Medical sciences Middle Aged motor fluctuation Neurology Nitriles - pharmacokinetics Nitriles - therapeutic use Parkinson Disease - blood Parkinson Disease - drug therapy Parkinson's disease pharmacodynamics pharmacokinetics Pharmacology. Drug treatments Retrospective Studies Severity of Illness Index Time Factors Toxicity: nervous system and muscle |
| Title | Pharmacokinetic-pharmacodynamic crossover comparison of two levodopa extension strategies |
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