Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Amount, type and storage of medicines in households – A survey for medicine users","authors":"Mella Louhisalmi,&nbsp;Piia Lavikainen,&nbsp;Kari Linden,&nbsp;Janne Martikainen,&nbsp;Johanna Timonen","doi":"10.1111/bcpt.14104","DOIUrl":"10.1111/bcpt.14104","url":null,"abstract":"<p>With increasing medicine use, more medicines are being stored at home, yet the understanding of household medicines remains limited. This study aimed to assess the amount, type and storage practices of medicines in households. It also explored the reasons for unnecessary or expired medicines, as well as the factors associated with the presence of expired medicines in a household. The online survey was conducted among loyal customers of University Pharmacy in June 2023 (<i>n</i> = 5004). The data were analysed for frequencies and percentages, and binary logistic regression was used to examine the association between background factors and expired medicines in households. On average, one household had 13.9 active, 2.8 unnecessary and 2.2 expired medicine packs. Medicines were typically stored in the kitchen (67.0%) and in cabinets (58.7%), and 40% were to be stored safely. The main reasons for unnecessary or expired medicines were improved health (39.2%), medication changes (31.9%) and oversized packs (28.0%). Households returning medicines biennially (odds ratio (OR): 2.85; 95% confidence interval (CI): 2.13–3.82) and those with many active medicines (OR: 2.14; 95% CI: 1.79–2.54) had expired medicines more often. The study showed that households had many medicines, highlighting the need for better storage and optimized packaging to improve safety, reduce waste and enhance rational pharmacotherapy.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"sGC stimulator (BAY 41-8543) combined with PDE9 inhibitor (BAY 73-6691) reduces renal fibrosis in 5/6 nephrectomized rats","authors":"Xin Chen,&nbsp;Denis Delić,&nbsp;Yvonne Liu,&nbsp;Yaochen Cao,&nbsp;Zeyu Zhang,&nbsp;Hongwei Wu,&nbsp;Mohamed M. S. Gaballa,&nbsp;Thomas Klein,&nbsp;Saban Elitok,&nbsp;Bernhard K. Krämer,&nbsp;Berthold Hocher","doi":"10.1111/bcpt.14103","DOIUrl":"10.1111/bcpt.14103","url":null,"abstract":"<p>Renal fibrosis is closely related to the prognosis of chronic kidney disease (CKD). The increase in cGMP reduces renal fibrosis. Soluble guanylate cyclase (sGC) and phosphodiesterase (PDE) are key enzymes that maintain cGMP levels. BAY 41–8543 (1 mg/kg/day) and/or BAY 73–6691 (1 mg/kg/day) were used to treat 5/6 nephrectomized rats for 13 weeks. 5/6 Nephrectomy caused an increase in cystatin C, proteinuria and glomerulosclerosis and renal interstitial fibrosis. Neither sGC stimulation nor PDE9 inhibition alone improved kidney function and morphology, whereas BAY 41–8543 in combination with BAY 73–6691 attenuated renal interstitial fibrosis. This beneficial effect could not be explained by alterations in blood pressure and the renal immune system. BAY 41–8543 in combination with BAY 73–6691 had no effect on renal macrophage, CD4 + T-cell and CD8 + T-cell in the late-stage of 5/6 nephrectomy. RNA sequencing revealed BAY 41–8543 in combination with BAY 73–6691 down-regulated the expression of fibrosis-related genes such as Collagen Type I Alpha 1, Collagen Type III Alpha 1 Chain and Collagen Type XIV Alpha 1 Chain. sGC stimulator combined with PDE9 inhibitor attenuated renal fibrosis in 5/6 nephrectomized rats by down-regulating fibrosis-related gene expression. This novel approach of using low-dose combination therapies to minimize side effects while maintaining therapeutic efficacy offers a promising strategy for the treatment of CKD.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dichloroacetate, a pyruvate dehydrogenase activator, alleviates high-fat-induced impairment of myogenic differentiation in skeletal muscles","authors":"Chuang-Yen Huang,&nbsp;I-Shan Han,&nbsp;Po-Shiuan Hsieh,&nbsp;Min-Chien Tsai,&nbsp;Hung-Che Chien","doi":"10.1111/bcpt.14102","DOIUrl":"10.1111/bcpt.14102","url":null,"abstract":"<p>Obesity-induced impairment of myogenic differentiation leads to muscle loss and sarcopenia. Pyruvate dehydrogenase (PDH) plays a crucial role in glucose metabolism and is associated with muscle differentiation. However, the effect of dichloroacetate (DCA), a PDH activator, on obesity-induced impairment of myogenic differentiation remains unknown. Here, we evaluated the effects of DCA treatment on high-fat intake-induced impairment of myogenic differentiation in C2C12 cells and C57BL/6 mice. In C2C12 cells, DCA treatment improved PDH activity that was reduced by palmitate (PAL) and decreased the lactate concentrations in the media. Additionally, DCA reversed PAL- and high-fat diet (HFD)-induced decrease in the expression of myoblast determination protein 1 (MyoD), myogenin (MyoG) and myosin heavy chain (MyHC) in C2C12 cells and C57BL/6 mice. To explore the possible mechanism, DCA treatment restored the levels of p-Akt, p-FoxO1, p-FoxO3a and p-p38 MAPK levels in PAL-treated C2C12 cells. Moreover, the protective effects of DCA were reversed by treatment with the Akt inhibitor MK2206 in C2C12 cells. In summary, DCA treatment alleviated high-fat intake-induced impairment of myogenic differentiation via Akt signalling, suggesting its potential in treating obesity-associated muscle loss and sarcopenia.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A nationwide Swedish retrospective study on poisoning deaths between the years 2000 and 2022","authors":"Elin Lindqvist,&nbsp;Jacob Hollenberg,&nbsp;Mattias Ringh,&nbsp;Per Nordberg,&nbsp;Henrik Druid,&nbsp;Leif Svensson,&nbsp;Sune Forsberg","doi":"10.1111/bcpt.14097","DOIUrl":"10.1111/bcpt.14097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Approximately 1% of Sweden's 90 000 annual deaths were reported caused by poisoning. In this study, we aim to describe this poisoning population's characteristics, autopsy frequency and results of toxicology testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>A national cohort study based on Swedish national registers. All deceased subjects older than 18 years with poisoning as the cause of death registered between 1 January 2000 and 31 December 2021 were included. Causes of death according to primary ICD-10 code were analysed along with the substances found in forensic chemistry testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 27 057 poisonous deaths during the study periods 2 018 495 adult deaths. Subjects deceased due to poisoning had a median age of 53 years, and 18 838 (70%) were men. A private home was the most reported location of death (52%). In total, 23 260 (87%) did undergo some sort post-mortem examination. Drugs (synthetic narcotics, opioids, heroin) caused 12 448 (46%) deaths, and alcohols explained 9056 cases (33%). Positive toxicological tests were found in 22 550 (83%) of the subjects. The most common separate substances were ethanol, zopiclone and nordazepam.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Poisoning caused 1.3% of Swedish deaths. Men in their 50s were the most common victims, and their deaths were often cause by synthetic narcotics, other opioids or alcohol. The autopsy frequency was lower than expected for poisonous deaths.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population pharmacokinetic modelling of cetirizine concentrations in human breast milk—A contribution from the ConcePTION project","authors":"Erik Melander,&nbsp;Elisabet I. Nielsen,&nbsp;Annika Lindqvist,&nbsp;Markus Hovd,&nbsp;Peggy Gandia,&nbsp;Alice Panchaud,&nbsp;Monia Guidi,&nbsp;Pieter Annaert,&nbsp;Pawel Baranczewski,&nbsp;Olav Spigset,&nbsp;Hedvig Nordeng","doi":"10.1111/bcpt.14100","DOIUrl":"10.1111/bcpt.14100","url":null,"abstract":"<p>Cetirizine is an antihistamine commonly used to treat allergic rhinitis and other allergic conditions. Cetirizine is often prescribed to breastfeeding mothers although there is limited information on infant exposure via breast milk. The aim of this study was to develop a popPK model based on data from a lactation study to predict cetirizine breast milk concentrations and estimate the relative infant dose (RID) in a breastfed infant. A popPK model was developed in NONMEM on data from a human lactation study including 35 women using cetirizine or levocetirizine while breastfeeding. Serial samples of breast milk were collected (n = 205) and the cetirizine concentrations quantified using a validated LC–MS/MS method. A one-compartment model of cetirizine in breast milk was developed and employed to calculate the relative infant dose (RID). Covariates related to the maternal characteristics and breastfeeding patterns were evaluated in the model; only milk sampling pumping duration was found to be a significant covariate, with an increasing pumping duration leading to an increased apparent milk volume of distribution (V_m). The mean RID was 1.99% with the highest RID being 3.36% at C_max. PopPK modelling could be used to estimate infant exposure to cetirizine via breast milk. The low predicted exposure in infants supports that cetirizine is compatible with breastfeeding.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of bariatric surgery on the pharmacokinetics of drugs used for attention-deficit hyperactivity disorder—A case series","authors":"Hege-Merete Krabseth,&nbsp;Magnus Strømmen,&nbsp;Arne Helland,&nbsp;Olav Spigset","doi":"10.1111/bcpt.14099","DOIUrl":"10.1111/bcpt.14099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Changes in gastrointestinal physiology following bariatric surgery may affect the pharmacokinetics of drugs. Data on the impact of bariatric surgery on drugs used for attention-deficit/hyperactivity disorder (ADHD) are limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In patients treated with ADHD medication and undergoing bariatric surgery, serial drug concentrations were measured for 24 h preoperatively and one, six and 12 months postoperatively. Primary outcome was change in area under the concentration-time curve from 0 to 24 h (AUC_0–24), with other pharmacokinetic variables as secondary outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight patients treated with lisdexamphetamine (<i>n</i> = 4), dexamphetamine (<i>n</i> = 1), methylphenidate (<i>n</i> = 1) and atomoxetine (<i>n</i> = 2) were included. In total, 409 samples were analysed. Patients underwent sleeve gastrectomy (<i>n</i> = 5) and Roux-en-Y gastric bypass (<i>n</i> = 3). AUC_0–24 and C_max of dexamphetamine increased after surgery in those using the prodrug lisdexamphetamine. There was no clear-cut reduction in t_max postoperatively. For ritalinic acid and atomoxetine, no changes in AUC_0–24 were observed, but for atomoxetine, a higher C_max and a shorter t_max were observed postoperatively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Bariatric surgery may increase the systemic exposure of dexamphetamine after intake of lisdexamphetamine. Patients using lisdexamphetamine should be followed with regard to adverse drug reactions after bariatric surgery, and, if available, therapeutic drug monitoring should be considered.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.14099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodegenerative disorders: Advances in neurobiology and new treatment perspectives","authors":"Sâmia Joca","doi":"10.1111/bcpt.14098","DOIUrl":"10.1111/bcpt.14098","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An extended substrate spectrum of the proton organic cation antiporter and relation to other cation transporters","authors":"Cauzar Ali Khan,&nbsp;Nicolai Kirsch,&nbsp;Jürgen Brockmöller,&nbsp;Kyra-Elisa Maria Redeker","doi":"10.1111/bcpt.14090","DOIUrl":"10.1111/bcpt.14090","url":null,"abstract":"<p>Most central nervous system (CNS) active drugs are organic cations, which need carrier proteins for efficient transfer through the blood–brain barrier (BBB). A genetically still unidentified proton organic cation (H⁺/OC) antiporter is found in several tissues, including endothelial cells of the BBB. We characterized the substrate spectrum of the H⁺/OC antiporter and the overlap in substrate spectrum with OCTN1, OCTN2 or OCT3 by screening 87 potential substrates for transport activity. Based on high antiport rates, 45 of the tested substances were substrates of the H⁺/OC antiporter. They included antidepressants (like tranylcypromine or nortriptyline), antipsychotics (like levomepromazine) and local anaesthetics. Concentration-dependent transport was confirmed for 38 of the substrates. Transport uptake depending on a pH gradient across the cell membrane confirmed that 43 drugs were indeed substrates of the H⁺/OC antiporter. However, the patterns of pH dependence differed between the substrates, possibly indicating different modes of transport or the existence of multiple antiporter proteins. The substrate overlap between the H⁺/OC antiporter and OCTN1, OCTN2 or OCT3 was minimal, indicating that the latter three are not the proteins underlying the H⁺/OC antiporter activity. Overall, about 50% of positively charged drugs may be substrates of the antiporter, which may be the most important membrane transport protein for many drugs.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 6","pages":"720-742"},"PeriodicalIF":2.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The active ingredient of Evodia rutaecarpa reduces inflammation in knee osteoarthritis rats through blocking calcium influx and NF-κB pathway","authors":"Yan Gao,&nbsp;Sixiang Wang,&nbsp;Yuehong Gao,&nbsp;Li Yang","doi":"10.1111/bcpt.14096","DOIUrl":"10.1111/bcpt.14096","url":null,"abstract":"<p>Chronic inflammation significantly contributes to the progression of osteoarthritis (OA), and an anti-inflammatory small molecule derived from medicinal herbs could be a potential drug candidate for OA. Herein, we investigated the function and mechanism of Evodiamine (EAE), the active ingredient from <i>Evodia rutaecarpa</i>, in chondrocytes and macrophages in vitro and in vivo. The cytotoxicity of EAE was determined using an MTT assay. And the anti-inflammatory and anti-extracellular matrix (ECM) degradation effects of EAE were investigated using qRT-PCR, western blot (WB), immunofluorescence (IF). Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES), Fluo-4 AM, IF and AutoDock were used to elucidate the molecular mechanisms and signalling pathways of the reducing-inflammatory properties of EAE on chondrocytes in vitro. Moreover, the effect of EAE on macrophage polarization was detected by IF and flow cytometry (FC). Ultimately, we explored the in vivo therapeutic efficacy of EAE in an anterior cruciate ligament transection (ACLT)-induced OA model. The finding demonstrated that EAE blocked the phosphorylation of IKBα and Ca²⁺ influx, thereby curbing inflammation and ECM degradation. Additionally, EAE can prevent the polarization towards the M1 phenotype. Thus, our findings suggest that EAE has great potential as a therapeutic drug for the treatment of OA.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 6","pages":"705-719"},"PeriodicalIF":2.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of weekly versus daily cholecalciferol for repleting serum vitamin D (25(OH)D) deficiency: A systematic review and meta-analysis of randomized controlled trials","authors":"Émilie Bortolussi-Courval,&nbsp;Connor Prosty,&nbsp;Jimin J. Lee,&nbsp;Lisa M. McCarthy,&nbsp;Emily G. McDonald,&nbsp;Todd C. Lee","doi":"10.1111/bcpt.14092","DOIUrl":"10.1111/bcpt.14092","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/rationale</h3>\u0000 \u0000 <p>Weekly cholecalciferol can replace daily supplementation to reduce pill burden in patients with complex medication regimens and hypovitaminosis D, but evidence supporting this switch is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We aimed to determine whether weekly cholecalciferol was superior to daily cholecalciferol to replete patients with hypovitaminosis D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a systematic review of randomized controlled trials involving participants with baseline hypovitaminosis D (&lt;30 ng/ml) comparing weekly <i>versus</i> daily cholecalciferol dosing and where serum cholecalciferol was measured within 120 days of starting treatment. We searched MEDLINE, CINAHL and EMBASE from inception to 7 May 2024. A random-effects meta-analysis evaluated the odds ratio for repletion of serum vitamin D levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Eight trials involving 542 patients were included in the analysis. Weekly and daily cholecalciferol were not significantly different in correcting hypovitaminosis D (OR = 1.5, 95% CI = 0.3–6.9, <i>p</i> = 0.6, favouring weekly dosing, <i>I</i>² = 85.3%). A sensitivity analysis excluding otherwise healthy patients had similar findings (OR = 0.8, 95% CI = 0.3–2.1, <i>p</i> = 0.6). Most studies were at risk of bias; the different doses being compared increased the heterogeneity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Limited direct evidence supports a switch from daily to weekly cholecalciferol dosing; however, weekly supplementation was not demonstrably worse at repleting levels and decreased a patient's daily pill burden.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"135 6","pages":"685-692"},"PeriodicalIF":2.7,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}