Drug Interaction Studies in the 21st Century: Research into Cytochrome P450s, Transporters, and Simulations Informing Their Role in Drug-drug Interactions

2007 ◽  
Vol 22 (4) ◽  
pp. 223-224 ◽  
Author(s):  
Hiroshi Yamazaki
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
21St Century ◽  
Cytochrome P450s ◽  
Interaction Studies

2020 FDA Drug-drug Interaction Guidance: A Comparison Analysis and Action Plan by Pharmaceutical Industrial Scientists

2020 ◽  
Vol 21 (6) ◽  
pp. 403-426 ◽  
Author(s):  
Sirimas Sudsakorn ◽  
Praveen Bahadduri ◽  
Jennifer Fretland ◽  
Chuang Lu
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Drug Interactions ◽  
Action Plan ◽  
European Medicines Agency ◽  
Cytochrome P450 Enzyme ◽  
Interaction Studies ◽  
P450 Enzyme ◽  
Us Fda

Background: In January 2020, the US FDA published two final guidelines, one entitled “In vitro Drug Interaction Studies - Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Guidance for Industry” and the other entitled “Clinical Drug Interaction Studies - Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Guidance for Industry”. These were updated from the 2017 draft in vitro and clinical DDI guidance. Methods: This study is aimed to provide an analysis of the updates along with a comparison of the DDI guidelines published by the European Medicines Agency (EMA) and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) along with the current literature. Results: The updates were provided in the final FDA DDI guidelines and explained the rationale of those changes based on the understanding from research and literature. Furthermore, a comparison among the FDA, EMA, and PMDA DDI guidelines are presented in Tables 1, 2 and 3. Conclusion: The new 2020 clinical DDI guidance from the FDA now has even higher harmonization with the guidance (or guidelines) from the EMA and PMDA. A comparison of DDI guidance from the FDA 2017, 2020, EMA, and PMDA on CYP and transporter based DDI, mathematical models, PBPK, and clinical evaluation of DDI is presented in this review.

Progress in the Consideration of Possible Sex Differences in Drug Interaction Studies

2019 ◽  
Vol 20 (2) ◽  
pp. 114-123 ◽  
Author(s):  
Panjasaram Naidoo ◽  
Manoranjenni Chetty
Keyword(s):  
Sex Differences ◽  
Drug Interaction ◽  
Drug Interactions ◽  
Clinical Studies ◽  
Qt Prolongation ◽  
Equal Proportion ◽  
Anecdotal Evidence ◽  
Interaction Studies ◽  
Males And Females ◽  
General Guidance

Background: Anecdotal evidence suggests that there may be sex differences in Drug-drug Interactions (DDI) involving specific drugs. Regulators have provided general guidance for the inclusion of females in clinical studies. Some clinical studies have reported sex differences in the Pharmacokinetics (PK) of CYP3A4 substrates, suggesting that DDI involving CYP3A4 substrates could potentially show sex differences. Objective: The aim of this review was to investigate whether recent prospective DDI studies have included both sexes and whether there was evidence for the presence or absence of sex differences with the DDIs. Methods: The relevant details from 156 drug interaction studies within 124 papers were extracted and evaluated. Results: Only eight studies (five papers) compared the outcome of the DDI between males and females. The majority of the studies had only male volunteers. Five studies had females only while 60 had males only, with 7.7% of the studies having an equal proportion of both sexes. Surprisingly, four studies did not specify the sex of the subjects. : Based on the limited number of studies comparing males and females, no specific trends or conclusions were evident. Sex differences in the interaction were reported between ketoconazole and midazolam as well as clarithromycin and midazolam. However, no sex difference was observed with the interaction between clarithromycin and triazolam or erythromycin and triazolam. No sex-related PK differences were observed with the interaction between ketoconazole and domperidone, although sex-related differences in QT prolongation were observed. Conclusion: This review has shown that only limited progress had been made with the inclusion of both sexes in DDI studies.

Drug interaction studies of esomeprazole with amoxicillin and clarithromycin

2001 ◽  
Vol 120 (5) ◽  
pp. A581-A581
Author(s):  
T ANDERSSON ◽  
L ASTRAZENECA ◽  
K ROHSS ◽  
M HASSANALIN
Keyword(s):  
Drug Interaction ◽  
Interaction Studies

Kajian Interaksi Obat Metformin pada Pasien Diabetes Mellitus

2019 ◽  
Vol 8 (2) ◽  
pp. 55-58
Author(s):  
Havizur Rahman ◽  
Teresia Anggi Octavia
Keyword(s):  
Diabetes Mellitus ◽  
Drug Interaction ◽  
Data Collection ◽  
Drug Interactions ◽  
Degenerative Disease ◽  
Moderate Severity ◽  
Purposive Sampling ◽  
Chronic Degenerative Disease ◽  
Over Time ◽  
Diabetes Melitus

Diabetes melitus merupakan penyakit degeneratif kronis yang apabila tidak ditangani dengan tepat, lama kelamaan bisa timbul berbagai komplikasi, ini cenderung menyebabkan pasien mendapatkan banyak obat dalam satu resep yang dapat menimbulkan interaksi antar obat. Tujuan dari penelitian ini adalah mengetahui persentase terjadinya interaksi obat metformin secara teori serta mengkaji efek yang mungkin timbul dan solusinya. Teknik pengambilan data dengan purpossive sampling, yaitu resep pasien rujuk balik yang menderita diabetes mellitus yang menggunakan metformin. Data yang diperoleh ditemukan bahwa obat yang berinteraksi dengan metformin dengan tingkat keparahan minor ialah sebesar 60%. Kemudian untuk tingkat keparahan moderat ialah sebesar 20%. Sedangkan untuk tingkat keparahan mayor tidak ditemukan. Dari tabel diatas juga dapat diketahui bahwa terdapat 4 obat yang saling berinteraksi dengan metformin, sedangkan untuk obat yang tidak saling berinteraksi dengan metformin terdapat 9 obat. Jumlah obat yang berinteraksi secara teori sebesar 6,85% dan yang tidak berinteraksi 93,15%. Terdapat interaksi obat metformin dengan beberapa obat yaitu furosemid, lisinopril, acarbose dan ramipril.   Kata kunci: interaksi obat, metformin, diabetes mellitus   STUDY OF METFORMIN INTERACTION IN MELLITUS DIABETES PATIENTS   ABSTRACT Mellitus is a chronic degenerative disease which if not handled properly, over time can arise various complications, this tends to cause patients to get many drugs in one recipe that can cause interactions between drugs. The purpose of this study is to determine percentage of metformin drug interactions in theory and examine the effects that may arise and solutions. Data collection techniques using purposive sampling, which is a recipe for reconciliation patients who suffer from diabetes mellitus using metformin. The data obtained it was found that drugs that interact with metformin with minor severity were 60%. Then for moderate severity is 20%. Whereas the major severity was not found. From the table above it can also be seen that there are 4 drugs that interact with metformin, while for drugs that do not interact with metformin there are 9 drugs. The number of drugs that interacted theoretically was 6.85% and 93.15% did not interact. An interaction of the drug metformin with several drugs namely furosemide, lisinopril, acarbose and ramipril.   Keywords: drug interaction, metformin, diabetes mellitus

Pharmacokinetic Drug-drug Interaction of Antibiotics Used in Sepsis Care in China

2020 ◽  
Vol 21 ◽  
Author(s):  
Xuan Yu ◽  
Zixuan Chu ◽  
Jian Li ◽  
Rongrong He ◽  
Yaya Wang ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Drug Interactions ◽  
Penicillin G ◽  
Literature Mining ◽  
Human Pharmacokinetics ◽  
P450 Enzyme ◽  
Drug Drug Interaction ◽  
Pharmacokinetic Drug ◽  
Sepsis Care

Background: Many antibiotics have a high potential for having an interaction with drugs, as perpetrator and/or victim, in critically ill patients, and particularly in sepsis patients. Methods: The aim of this review is to summarize the pharmacokinetic drug-drug interaction (DDI) of 45 antibiotics commonly used in sepsis care in China. Literature mining was conducted to obtain human pharmacokinetics/dispositions of the antibiotics, their interactions with drug metabolizing enzymes or transporters, and their associated clinical drug interactions. Potential DDI is indicated by a DDI index > 0.1 for inhibition or a treated-cell/untreated-cell ratio of enzyme activity being > 2 for induction. Results: The literature-mined information on human pharmacokinetics of the identified antibiotics and their potential drug interactions is summarized. Conclusion: Antibiotic-perpetrated drug interactions, involving P450 enzyme inhibition, have been reported for four lipophilic antibacterials (ciprofloxacin, erythromycin, trimethoprim, and trimethoprim-sulfamethoxazole) and three lipophilic antifungals (fluconazole, itraconazole, and voriconazole). In addition, seven hydrophilic antibacterials (ceftriaxone, cefamandole, piperacillin, penicillin G, amikacin, metronidazole, and linezolid) inhibit drug transporters in vitro. Despite no reported clinical PK drug interactions with the transporters, caution is advised in the use of these antibacterials. Eight hydrophilic antibacterials (all β-lactams; meropenem, cefotaxime, cefazolin, piperacillin, ticarcillin, penicillin G, ampicillin, and flucloxacillin), are potential victims of drug interactions due to transporter inhibition. Rifampin is reported to perpetrate drug interactions by inducing CYP3A or inhibiting OATP1B; it is also reported to be a victim of drug interactions, due to the dual inhibition of CYP3A4 and OATP1B by indinavir. In addition, three antifungals (caspofungin, itraconazole, and voriconazole) are reported to be victims of drug interactions because of P450 enzyme induction. Reports for other antibiotics acting as victims in drug interactions are scarce.

scholarly journals Herb–Drug Interactions: Worlds Intersect with the Patient at the Center

Medicines ◽  
2021 ◽  
Vol 8 (8) ◽  
pp. 44
Author(s):  
Mary Beth Babos ◽  
Michelle Heinan ◽  
Linda Redmond ◽  
Fareeha Moiz ◽  
Joao Victor Souza-Peres ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Case Report ◽  
Drug Interactions ◽  
Clinical Studies ◽  
Drug Information ◽  
Case Reports ◽  
Full Information ◽  
Information Need ◽  
Herbal Products ◽  
Reduce Risk

This review examines three bodies of literature related to herb–drug interactions: case reports, clinical studies, evaluations found in six drug interaction checking resources. The aim of the study is to examine the congruity of resources and to assess the degree to which case reports signal for further study. A qualitative review of case reports seeks to determine needs and perspectives of case report authors. Methods: Systematic search of Medline identified clinical studies and case reports of interacting herb–drug combinations. Interacting herb–drug pairs were searched in six drug interaction resources. Case reports were analyzed qualitatively for completeness and to identify underlying themes. Results: Ninety-nine case-report documents detailed 107 cases. Sixty-five clinical studies evaluated 93 mechanisms of interaction relevant to herbs reported in case studies, involving 30 different herbal products; 52.7% of these investigations offered evidence supporting reported reactions. Cohen’s kappa found no agreement between any interaction checker and case report corpus. Case reports often lacked full information. Need for further information, attitudes about herbs and herb use, and strategies to reduce risk from interaction were three primary themes in the case report corpus. Conclusions: Reliable herb–drug information is needed, including open and respectful discussion with patients.

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