Effect of CYP1A2, CYP2D6, and CYP3A4 Variation on Antipsychotic Treatment Outcomes
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| Publicado en: | Pharmaceuticals vol. 18, no. 6 (2025), p. 892-919 |
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| Autor principal: | |
| Otros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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MDPI AG
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| Acceso en línea: | Citation/Abstract Full Text + Graphics Full Text - PDF |
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| 024 | 7 | |a 10.3390/ph18060892 |2 doi | |
| 035 | |a 3223931375 | ||
| 045 | 2 | |b d20250101 |b d20251231 | |
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| 100 | 1 | |a Varney, Lauren |u Division of Psychiatry, University College London, London W1T 7NF, UK; s.murtough@ucl.ac.uk (S.M.); m.cotic@ucl.ac.uk (M.C.); r.abidoph@ucl.ac.uk (R.A.); noushin.khani.21@ucl.ac.uk (N.S.K.); alvin.richards-belle.21@ucl.ac.uk (A.R.-B.); maria.richards-brown.23@ucl.ac.uk (M.R.-B.); daisy.mills.23@ucl.ac.uk (D.M.); daniele.panconesi.20@ucl.ac.uk (D.P.) | |
| 245 | 1 | |a Effect of <i>CYP1A2</i>, <i>CYP2D6</i>, and <i>CYP3A4</i> Variation on Antipsychotic Treatment Outcomes | |
| 260 | |b MDPI AG |c 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Background/Objectives: Antipsychotic treatment response varies considerably between individuals, with one potential reason being genetic variation affecting the cytochrome P450 enzymes that metabolise them. Methods: With a diverse sample of 453 participants, we studied the influence of CYP1A2, CYP2D6, and CYP3A4 variation on three antipsychotic treatment outcomes: participant-reported adverse antipsychotic drug reactions, health-related quality of life, and the dose of antipsychotic medication prescribed. These measures were taken from the baseline assessment, before a pharmacogenetic intervention was delivered. Results: Over half of our sample (62.9%) were carriers of an allele associated with altered metabolism of antipsychotic medications on CYP2D6 or CYP3A4, the two genes with pharmacogenetic guidelines for antipsychotic medications. Ultrarapid CYP2D6 metabolisers reported significantly lower levels of adverse antipsychotic drug reactions than normal CYP2D6 metabolisers (mean difference: −11.1; 95% confidence interval [CI]: −18.9, −3.3; p = 0.00575). There was also suggestive evidence of lower quality of life scores in those carrying one (mean difference: −0.0863; 95% CI: −0.1806, 0.0081; p = 0.0731) or two copies (mean difference: −0.0803; 95% CI: −0.1734, 0.0129; p = 0.0914) of the CYP1A2*30-inducible allele. Conclusions: Our findings suggest that even when looking at a small number of cytochrome P450 genes, carrying an allele associated with altered antipsychotic medication metabolism is relatively common. We also found evidence that the CYP genotype can influence antipsychotic treatment outcomes, specifically adverse drug reactions and quality of life scores. | |
| 610 | 4 | |a Food & Drug Administration--FDA | |
| 651 | 4 | |a United Kingdom--UK | |
| 653 | |a Quality of life | ||
| 653 | |a Schizophrenia | ||
| 653 | |a Mental disorders | ||
| 653 | |a Psychotropic drugs | ||
| 653 | |a Psychosis | ||
| 653 | |a Side effects | ||
| 653 | |a Mental depression | ||
| 653 | |a Licenses | ||
| 653 | |a Bipolar disorder | ||
| 653 | |a Metabolism | ||
| 653 | |a Mental health | ||
| 653 | |a Ethnicity | ||
| 653 | |a Genes | ||
| 653 | |a Enzymes | ||
| 653 | |a Antipsychotics | ||
| 653 | |a Clinical outcomes | ||
| 653 | |a Drug dosages | ||
| 700 | 1 | |a Murtough, Stephen |u Division of Psychiatry, University College London, London W1T 7NF, UK; s.murtough@ucl.ac.uk (S.M.); m.cotic@ucl.ac.uk (M.C.); r.abidoph@ucl.ac.uk (R.A.); noushin.khani.21@ucl.ac.uk (N.S.K.); alvin.richards-belle.21@ucl.ac.uk (A.R.-B.); maria.richards-brown.23@ucl.ac.uk (M.R.-B.); daisy.mills.23@ucl.ac.uk (D.M.); daniele.panconesi.20@ucl.ac.uk (D.P.) | |
| 700 | 1 | |a Cotic Marius |u Division of Psychiatry, University College London, London W1T 7NF, UK; s.murtough@ucl.ac.uk (S.M.); m.cotic@ucl.ac.uk (M.C.); r.abidoph@ucl.ac.uk (R.A.); noushin.khani.21@ucl.ac.uk (N.S.K.); alvin.richards-belle.21@ucl.ac.uk (A.R.-B.); maria.richards-brown.23@ucl.ac.uk (M.R.-B.); daisy.mills.23@ucl.ac.uk (D.M.); daniele.panconesi.20@ucl.ac.uk (D.P.) | |
| 700 | 1 | |a Abidoph Rosemary |u Division of Psychiatry, University College London, London W1T 7NF, UK; s.murtough@ucl.ac.uk (S.M.); m.cotic@ucl.ac.uk (M.C.); r.abidoph@ucl.ac.uk (R.A.); noushin.khani.21@ucl.ac.uk (N.S.K.); alvin.richards-belle.21@ucl.ac.uk (A.R.-B.); maria.richards-brown.23@ucl.ac.uk (M.R.-B.); daisy.mills.23@ucl.ac.uk (D.M.); daniele.panconesi.20@ucl.ac.uk (D.P.) | |
| 700 | 1 | |a Chan, Lian |u Department of Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1DZ, UK; lian.chan.22@ucl.ac.uk | |
| 700 | 1 | |a Saadullah Khani Noushin |u Division of Psychiatry, University College London, London W1T 7NF, UK; s.murtough@ucl.ac.uk (S.M.); m.cotic@ucl.ac.uk (M.C.); r.abidoph@ucl.ac.uk (R.A.); noushin.khani.21@ucl.ac.uk (N.S.K.); alvin.richards-belle.21@ucl.ac.uk (A.R.-B.); maria.richards-brown.23@ucl.ac.uk (M.R.-B.); daisy.mills.23@ucl.ac.uk (D.M.); daniele.panconesi.20@ucl.ac.uk (D.P.) | |
| 700 | 1 | |a Richards-Belle, Alvin |u Division of Psychiatry, University College London, London W1T 7NF, UK; s.murtough@ucl.ac.uk (S.M.); m.cotic@ucl.ac.uk (M.C.); r.abidoph@ucl.ac.uk (R.A.); noushin.khani.21@ucl.ac.uk (N.S.K.); alvin.richards-belle.21@ucl.ac.uk (A.R.-B.); maria.richards-brown.23@ucl.ac.uk (M.R.-B.); daisy.mills.23@ucl.ac.uk (D.M.); daniele.panconesi.20@ucl.ac.uk (D.P.) | |
| 700 | 1 | |a Richards-Brown, Maria |u Division of Psychiatry, University College London, London W1T 7NF, UK; s.murtough@ucl.ac.uk (S.M.); m.cotic@ucl.ac.uk (M.C.); r.abidoph@ucl.ac.uk (R.A.); noushin.khani.21@ucl.ac.uk (N.S.K.); alvin.richards-belle.21@ucl.ac.uk (A.R.-B.); maria.richards-brown.23@ucl.ac.uk (M.R.-B.); daisy.mills.23@ucl.ac.uk (D.M.); daniele.panconesi.20@ucl.ac.uk (D.P.) | |
| 700 | 1 | |a Mills, Daisy |u Division of Psychiatry, University College London, London W1T 7NF, UK; s.murtough@ucl.ac.uk (S.M.); m.cotic@ucl.ac.uk (M.C.); r.abidoph@ucl.ac.uk (R.A.); noushin.khani.21@ucl.ac.uk (N.S.K.); alvin.richards-belle.21@ucl.ac.uk (A.R.-B.); maria.richards-brown.23@ucl.ac.uk (M.R.-B.); daisy.mills.23@ucl.ac.uk (D.M.); daniele.panconesi.20@ucl.ac.uk (D.P.) | |
| 700 | 1 | |a Panconesi Daniele |u Division of Psychiatry, University College London, London W1T 7NF, UK; s.murtough@ucl.ac.uk (S.M.); m.cotic@ucl.ac.uk (M.C.); r.abidoph@ucl.ac.uk (R.A.); noushin.khani.21@ucl.ac.uk (N.S.K.); alvin.richards-belle.21@ucl.ac.uk (A.R.-B.); maria.richards-brown.23@ucl.ac.uk (M.R.-B.); daisy.mills.23@ucl.ac.uk (D.M.); daniele.panconesi.20@ucl.ac.uk (D.P.) | |
| 700 | 1 | |a Dawda Yogita |u Central and North West London NHS Foundation Trust, 350 Euston Road, Regent’s Place, London NW1 3AX, UK; yogita.dawda@nhs.net (Y.D.); rebecca.griffiths31@nhs.net (R.G.); s.senthilkumar@nhs.net (S.S.); girijakottalgi@nhs.net (G.K.); | |
| 700 | 1 | |a Sharma, Parveen |u Greater Manchester Mental Health NHS Foundation Trust, Bury New Road, Prestwich, Manchester M25 3BL, UK; parveen.sharma@gmmh.nhs.uk (P.S.); jennifer.mcroberts@gmmh.nhs.uk (J.M.); bethany.pastor@gmmh.nhs.uk (B.P.); carmel.thomas@gmmh.nhs.uk (C.T.); nithya.anandan@gmmh.nhs.uk (N.A.); georgy.pius@gmmh.nhs.uk (G.P.) | |
| 700 | 1 | |a Shah, Chetan |u Hertfordshire Partnership University NHS Foundation Trust, The Colonnades, Beaconsfield Road, Hatfield AL10 8YE, UK; chetanshah@nhs.net (C.S.); sabrina.richards5@nhs.net (S.R.) | |
| 700 | 1 | |a Secchi Agostina |u Kent and Medway NHS and Social Care Partnership Trust, Farm Villa, Hermitage Lane, Maidstone ME16 9PH, UK; a.secchi@nhs.net (A.S.); alison.welfare-wilson@nhs.net (A.W.-W.); victoria.clark11@nhs.net (V.C.) | |
| 700 | 1 | |a Nilforooshan Ramin |u Surrey and Borders Partnership NHS Foundation Trust, 18 Mole Business Park, Randalls Road, Leatherhead, Surrey KT22 7AD, UK; ramin.nilforooshan@sabp.nhs.uk (R.N.); sai-bo.cheung@sabp.nhs.uk (S.-B.C.) | |
| 700 | 1 | |a Mudholkar Santosh |u West London NHS Trust, 1 Armstrong Way, Southall UB2 4SD, UKreanne.anad@nhs.net (R.A.); r.laczik@nhs.net (R.L.) | |
| 700 | 1 | |a Murdoch, Rosie |u <label>10</label>Berkshire Healthcare NHS Foundation Trust, London House, London Road, Bracknell RG12 2UT, UK; rosie2.murdoch@outlook.com (R.M.); sharif.ghali@berkshire.nhs.uk (S.G.) | |
| 700 | 1 | |a Molai Jazmin |u North London NHS Foundation Trust, 4th Floor, East Wing, St Pancras Hospital, 4 St Pancras Way, London NW1 0PE, UK; jazmin.molai2@nhs.net (J.M.); alex.berry6@nhs.net (A.J.B.); joanna.curwen@nhs.net (J.C.); | |
| 700 | 1 | |a Griffiths, Rebecca |u Central and North West London NHS Foundation Trust, 350 Euston Road, Regent’s Place, London NW1 3AX, UK; yogita.dawda@nhs.net (Y.D.); rebecca.griffiths31@nhs.net (R.G.); s.senthilkumar@nhs.net (S.S.); girijakottalgi@nhs.net (G.K.); | |
| 700 | 1 | |a Senthilkumar Suruthy |u Central and North West London NHS Foundation Trust, 350 Euston Road, Regent’s Place, London NW1 3AX, UK; yogita.dawda@nhs.net (Y.D.); rebecca.griffiths31@nhs.net (R.G.); s.senthilkumar@nhs.net (S.S.); girijakottalgi@nhs.net (G.K.); | |
| 700 | 1 | |a Blake, Helen |u <label>11</label>Essex Partnership University NHS Foundation Trust, The Lodge, Lodge Approach, Runwell, Wickford SS11 7XX, UK; helen.blake5@nhs.net | |
| 700 | 1 | |a Lankshear, Steve |u Greater Manchester Mental Health NHS Foundation Trust, Bury New Road, Prestwich, Manchester M25 3BL, UK; parveen.sharma@gmmh.nhs.uk (P.S.); jennifer.mcroberts@gmmh.nhs.uk (J.M.); bethany.pastor@gmmh.nhs.uk (B.P.); carmel.thomas@gmmh.nhs.uk (C.T.); nithya.anandan@gmmh.nhs.uk (N.A.); georgy.pius@gmmh.nhs.uk (G.P.) | |
| 700 | 1 | |a McRoberts, Jennifer |u Greater Manchester Mental Health NHS Foundation Trust, Bury New Road, Prestwich, Manchester M25 3BL, UK; parveen.sharma@gmmh.nhs.uk (P.S.); jennifer.mcroberts@gmmh.nhs.uk (J.M.); bethany.pastor@gmmh.nhs.uk (B.P.); carmel.thomas@gmmh.nhs.uk (C.T.); nithya.anandan@gmmh.nhs.uk (N.A.); georgy.pius@gmmh.nhs.uk (G.P.) | |
| 700 | 1 | |a Pastor, Bethany |u Greater Manchester Mental Health NHS Foundation Trust, Bury New Road, Prestwich, Manchester M25 3BL, UK; parveen.sharma@gmmh.nhs.uk (P.S.); jennifer.mcroberts@gmmh.nhs.uk (J.M.); bethany.pastor@gmmh.nhs.uk (B.P.); carmel.thomas@gmmh.nhs.uk (C.T.); nithya.anandan@gmmh.nhs.uk (N.A.); georgy.pius@gmmh.nhs.uk (G.P.) | |
| 700 | 1 | |a Carmel, Thomas |u Greater Manchester Mental Health NHS Foundation Trust, Bury New Road, Prestwich, Manchester M25 3BL, UK; parveen.sharma@gmmh.nhs.uk (P.S.); jennifer.mcroberts@gmmh.nhs.uk (J.M.); bethany.pastor@gmmh.nhs.uk (B.P.); carmel.thomas@gmmh.nhs.uk (C.T.); nithya.anandan@gmmh.nhs.uk (N.A.); georgy.pius@gmmh.nhs.uk (G.P.) | |
| 700 | 1 | |a Richards, Sabrina |u Hertfordshire Partnership University NHS Foundation Trust, The Colonnades, Beaconsfield Road, Hatfield AL10 8YE, UK; chetanshah@nhs.net (C.S.); sabrina.richards5@nhs.net (S.R.) | |
| 700 | 1 | |a Welfare-Wilson, Alison |u Kent and Medway NHS and Social Care Partnership Trust, Farm Villa, Hermitage Lane, Maidstone ME16 9PH, UK; a.secchi@nhs.net (A.S.); alison.welfare-wilson@nhs.net (A.W.-W.); victoria.clark11@nhs.net (V.C.) | |
| 700 | 1 | |a Sai-Bo, Cheung |u Surrey and Borders Partnership NHS Foundation Trust, 18 Mole Business Park, Randalls Road, Leatherhead, Surrey KT22 7AD, UK; ramin.nilforooshan@sabp.nhs.uk (R.N.); sai-bo.cheung@sabp.nhs.uk (S.-B.C.) | |
| 700 | 1 | |a Cox, Rebecca |u <label>12</label>South West London and St George’s Mental Health NHS Trust, Springfield University Hospital, Trinity Building, 15 Springfield Drive, London SW17 0YF, UK; rebecca.cox@swlstg.nhs.uk (R.C.); anita.jibero@swlstg.nhs.uk (A.C.J.); amir.bashir@swlstg.nhs.uk (A.B.) | |
| 700 | 1 | |a Jibero, Anita Chinazam |u <label>12</label>South West London and St George’s Mental Health NHS Trust, Springfield University Hospital, Trinity Building, 15 Springfield Drive, London SW17 0YF, UK; rebecca.cox@swlstg.nhs.uk (R.C.); anita.jibero@swlstg.nhs.uk (A.C.J.); amir.bashir@swlstg.nhs.uk (A.B.) | |
| 700 | 1 | |a Anad Reanne |u West London NHS Trust, 1 Armstrong Way, Southall UB2 4SD, UKreanne.anad@nhs.net (R.A.); r.laczik@nhs.net (R.L.) | |
| 700 | 1 | |a Laczik Rebeka |u West London NHS Trust, 1 Armstrong Way, Southall UB2 4SD, UKreanne.anad@nhs.net (R.A.); r.laczik@nhs.net (R.L.) | |
| 700 | 1 | |a Ghali Sharif |u <label>10</label>Berkshire Healthcare NHS Foundation Trust, London House, London Road, Bracknell RG12 2UT, UK; rosie2.murdoch@outlook.com (R.M.); sharif.ghali@berkshire.nhs.uk (S.G.) | |
| 700 | 1 | |a Berry, Alex J |u North London NHS Foundation Trust, 4th Floor, East Wing, St Pancras Hospital, 4 St Pancras Way, London NW1 0PE, UK; jazmin.molai2@nhs.net (J.M.); alex.berry6@nhs.net (A.J.B.); joanna.curwen@nhs.net (J.C.); | |
| 700 | 1 | |a Curwen, Joanna |u North London NHS Foundation Trust, 4th Floor, East Wing, St Pancras Hospital, 4 St Pancras Way, London NW1 0PE, UK; jazmin.molai2@nhs.net (J.M.); alex.berry6@nhs.net (A.J.B.); joanna.curwen@nhs.net (J.C.); | |
| 700 | 1 | |a Koye, Odutoye |u North London NHS Foundation Trust, 4th Floor, East Wing, St Pancras Hospital, 4 St Pancras Way, London NW1 0PE, UK; jazmin.molai2@nhs.net (J.M.); alex.berry6@nhs.net (A.J.B.); joanna.curwen@nhs.net (J.C.); | |
| 700 | 1 | |a Kottalgi Girija |u Central and North West London NHS Foundation Trust, 350 Euston Road, Regent’s Place, London NW1 3AX, UK; yogita.dawda@nhs.net (Y.D.); rebecca.griffiths31@nhs.net (R.G.); s.senthilkumar@nhs.net (S.S.); girijakottalgi@nhs.net (G.K.); | |
| 700 | 1 | |a Williams, Sally |u Central and North West London NHS Foundation Trust, 350 Euston Road, Regent’s Place, London NW1 3AX, UK; yogita.dawda@nhs.net (Y.D.); rebecca.griffiths31@nhs.net (R.G.); s.senthilkumar@nhs.net (S.S.); girijakottalgi@nhs.net (G.K.); | |
| 700 | 1 | |a Wong, Solomon |u Central and North West London NHS Foundation Trust, 350 Euston Road, Regent’s Place, London NW1 3AX, UK; yogita.dawda@nhs.net (Y.D.); rebecca.griffiths31@nhs.net (R.G.); s.senthilkumar@nhs.net (S.S.); girijakottalgi@nhs.net (G.K.); | |
| 700 | 1 | |a Anandan Nithya |u Greater Manchester Mental Health NHS Foundation Trust, Bury New Road, Prestwich, Manchester M25 3BL, UK; parveen.sharma@gmmh.nhs.uk (P.S.); jennifer.mcroberts@gmmh.nhs.uk (J.M.); bethany.pastor@gmmh.nhs.uk (B.P.); carmel.thomas@gmmh.nhs.uk (C.T.); nithya.anandan@gmmh.nhs.uk (N.A.); georgy.pius@gmmh.nhs.uk (G.P.) | |
| 700 | 1 | |a Pius Georgy |u Greater Manchester Mental Health NHS Foundation Trust, Bury New Road, Prestwich, Manchester M25 3BL, UK; parveen.sharma@gmmh.nhs.uk (P.S.); jennifer.mcroberts@gmmh.nhs.uk (J.M.); bethany.pastor@gmmh.nhs.uk (B.P.); carmel.thomas@gmmh.nhs.uk (C.T.); nithya.anandan@gmmh.nhs.uk (N.A.); georgy.pius@gmmh.nhs.uk (G.P.) | |
| 700 | 1 | |a Ajiteru Tonye |u Kent and Medway NHS and Social Care Partnership Trust, Farm Villa, Hermitage Lane, Maidstone ME16 9PH, UK; a.secchi@nhs.net (A.S.); alison.welfare-wilson@nhs.net (A.W.-W.); victoria.clark11@nhs.net (V.C.) | |
| 700 | 1 | |a Clark, Victoria |u Kent and Medway NHS and Social Care Partnership Trust, Farm Villa, Hermitage Lane, Maidstone ME16 9PH, UK; a.secchi@nhs.net (A.S.); alison.welfare-wilson@nhs.net (A.W.-W.); victoria.clark11@nhs.net (V.C.) | |
| 700 | 1 | |a van Driel Philip |u <label>14</label>Somerset NHS Foundation Trust, The Bridge, Priory Park, Wells BA5 1TJ, UK; philip.vandriel@somersetft.nhs.uk | |
| 700 | 1 | |a Bashir Amir |u <label>12</label>South West London and St George’s Mental Health NHS Trust, Springfield University Hospital, Trinity Building, 15 Springfield Drive, London SW17 0YF, UK; rebecca.cox@swlstg.nhs.uk (R.C.); anita.jibero@swlstg.nhs.uk (A.C.J.); amir.bashir@swlstg.nhs.uk (A.B.) | |
| 700 | 1 | |a Court, Samantha |u <label>15</label>West Midlands Regional Genetics Laboratory, Birmingham Woman’s and Children’s NHS Foundation Trust, Birmingham B15 2TG, UK; samantha.court2@nhs.net (S.C.); minerva.pawsey@nhs.net (M.P.); anna.skowronska@nhs.net (A.S.); jessica.woodley2@nhs.net (J.W.) | |
| 700 | 1 | |a Pawsey Minerva |u <label>15</label>West Midlands Regional Genetics Laboratory, Birmingham Woman’s and Children’s NHS Foundation Trust, Birmingham B15 2TG, UK; samantha.court2@nhs.net (S.C.); minerva.pawsey@nhs.net (M.P.); anna.skowronska@nhs.net (A.S.); jessica.woodley2@nhs.net (J.W.) | |
| 700 | 1 | |a Skowronska Anna |u <label>15</label>West Midlands Regional Genetics Laboratory, Birmingham Woman’s and Children’s NHS Foundation Trust, Birmingham B15 2TG, UK; samantha.court2@nhs.net (S.C.); minerva.pawsey@nhs.net (M.P.); anna.skowronska@nhs.net (A.S.); jessica.woodley2@nhs.net (J.W.) | |
| 700 | 1 | |a Woodley, Jessica |u <label>15</label>West Midlands Regional Genetics Laboratory, Birmingham Woman’s and Children’s NHS Foundation Trust, Birmingham B15 2TG, UK; samantha.court2@nhs.net (S.C.); minerva.pawsey@nhs.net (M.P.); anna.skowronska@nhs.net (A.S.); jessica.woodley2@nhs.net (J.W.) | |
| 700 | 1 | |a Bramon Elvira |u Division of Psychiatry, University College London, London W1T 7NF, UK; s.murtough@ucl.ac.uk (S.M.); m.cotic@ucl.ac.uk (M.C.); r.abidoph@ucl.ac.uk (R.A.); noushin.khani.21@ucl.ac.uk (N.S.K.); alvin.richards-belle.21@ucl.ac.uk (A.R.-B.); maria.richards-brown.23@ucl.ac.uk (M.R.-B.); daisy.mills.23@ucl.ac.uk (D.M.); daniele.panconesi.20@ucl.ac.uk (D.P.) | |
| 773 | 0 | |t Pharmaceuticals |g vol. 18, no. 6 (2025), p. 892-919 | |
| 786 | 0 | |d ProQuest |t Research Library | |
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