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Conversion of Natural Products from Renewable Resources in Pharmaceuticals by Cytochromes P450
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Giovanna Di Nardo, Gianfranco Gilardi
Vitamin D2 (VD2) is physiologically produced from ergosterol in yeast or fungi, while VD3 is produced from 7-deoxycholesterol in mammals. The bioactive forms of vitamin D2 and D3, as well as their analogs, have been employed for the clinical treatment of different diseases including rickets, osteoporosis, hyperparathyroidism, and cancers. Paricalcitol (19-nor-1,25D2) and doxercalciferol (1α(OH)D2) that are vitamin D2 analogs, are currently used as drugs for the treatment of secondary hyperparathyroidism (Bover et al., 2014) and paricalcitol was shown to have anticancer activity (Alagbala et al., 2006; Chodyński et al., 2002).
P
Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
After oral administration of 3H-paricalcitol, only about 2% of the dose was eliminated unchanged in the faeces, and no parent drug found in the urine. Approximately 70% of the radioactivity was eliminated in the faeces and 18% was recovered in the urine. Most of the systemic exposure was from the parent drug.
Main Classes of Drugs
Published in Jerome Z. Litt, Neil H. Shear, Litt's Drug Eruption & Reaction Manual, 2017
Vitamin D receptor agonistDihydrotachysterolDoxercalciferolParicalcitol
Current treatment options for secondary hyperparathyroidism in patients with stage 3 to 4 chronic kidney disease and vitamin D deficiency
Published in Expert Opinion on Drug Safety, 2021
Andrea Galassi, Paola Ciceri, Giulia Porata, Rossella Iatrino, Giulia Boni Brivio, Eliana Fasulo, Lorenza Magagnoli, Andrea Stucchi, Michela Frittoli, Anila Cara, Mario Cozzolino
Selective VDRA, as paricalcitol, have been purposed for treating SHPT due to their capability to suppress PTH synthesis with minor impact on intestinal absorption phosphate and calcium absorption, compared with nonselective VDRA, as calcitriol, doxercalciferol or alfacalcidol (Table 1) [8]. Forty-five patients with stage 3–4 CKD patients and PTH levels > 120 pg/ml ml were randomized to calcitriol 0.25 mcg/day against paricalcitol 1 mcg/day for 24 weeks (Table 3) [74]. Despite similar PTH absolute levels at the study end, paricalcitol was associated with significantly higher rate of patients achieving 40% and 60% PTH reduction. Significant increase in serum Ca and P levels was observed in both arms, although being lower than 0.5 mg/dl and reversible after drug withdrawal.
Recent advances in drug discovery for diabetic kidney disease
Published in Expert Opinion on Drug Discovery, 2021
Chhanda Charan Danta, Andrew N. Boa, Sunil Bhandari, Thozhukat Sathyapalan, Shang-Zhong Xu
Over the last two decades, RAAS inhibitors have been the first-line treatment choice due to their successful clinical results [13]. Clinical trials on ACE inhibitors, such as captopril, and ARBs, including losartan and irbesartan, have demonstrated positive outcomes in decreasing albuminuria in DKD patients [74–77]. However, it has been reported that in clinical trials paricalcitol fails to show a renoprotective effect [78]. RAAS inhibitors have been shown to merely slow the progression of DKD, and some diabetic patients have still progressed to CKD and ESRD [13]. Inclusion of a mineralocorticoid receptor (MR) antagonist with ACE or ARB inhibitor regimen is beneficial in decreasing albuminuria, inflammation, and kidney fibrosis in patients with DKD. The risk of hyperkalemia due to MR antagonists can be lowered using novel non-steroidal MR antagonist such as finerenone, which is an MR antagonist. Recent trials with finerenone showed reductions in proteinuria, kidney failure and DKD progression [79]. In another clinical trial, finerenone also showed to reduce cardiovascular mortality and morbidity in DKD patients [80]. Some other MR antagonist such as spironolactone has been tested in combination with antidiabetic/renoprotective/antihypertensive drugs which showed positive results in reducing DKD progression and lowering proteinuria [81]. The finerenone is still under phase 3 clinical trial with T2DM patients to evaluate its efficacy in long-term for DKD [82]. Therefore, further investigation is still required to find better therapeutic candidates for this class of drug.
Urinary peptidomics in kidney disease and drug research
Published in Expert Opinion on Drug Discovery, 2018
Magdalena Krochmal, Joost P Schanstra, Harald Mischak
Perez et al. investigated the urinary peptidome of kidney transplant patients treated with paricalcitol [46] or atorvastatin [47] to monitor for pleiotropic effects associated with posttransplant treatment of secondary hyperparathyroidism and dyslipidemia. The assessment of urinary peptide changes in paricalcitol-treated patients indicated stabilization of the peptide content in comparison to untreated patients [46]. Levels of parathyroid hormone decreased in treated patients and a specific peptide of m/z 4568 was decreased after treatment; however, this decrease was not correlated with kidney function. In contrast, treatment with atorvastatin was confirmed to affect lipid profiles, but did not induce changes in urinary peptidome in kidney graft recipients [47]. Overall, both studies indicate the potential of peptidomics analysis for drug therapy monitoring and research on the molecular mechanism of specific drugs.