References of "Expert Opinion on Drug Metabolism & Toxicology"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailEvaluating SGLT2 inhibitors for type 2 diabetes: pharmacokinetic and toxicological considerations.
Scheen, André ULg

in Expert opinion on drug metabolism & toxicology (2014)

Introduction: Inhibitors of sodium-glucose cotransporters type 2 (SGLT2), which increase urinary glucose excretion independently of insulin, are proposed as a novel approach for the management of type 2 ... [more ▼]

Introduction: Inhibitors of sodium-glucose cotransporters type 2 (SGLT2), which increase urinary glucose excretion independently of insulin, are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Areas covered: An extensive literature search was performed to analyze the pharmacokinetic characteristics, toxicological issues and safety concerns of SGLT2 inhibitors in humans. This review focuses on three compounds (dapagliflozin, canagliflozin, empagliflozin) with results obtained in healthy volunteers (including drug-drug interactions), patients with T2DM (single dose and multiple doses) and special populations (those with renal or hepatic impairment). Expert opinion: The three pharmacological agents share an excellent oral bioavailability, long half-life allowing once-daily administration, low accumulation index and renal clearance, the absence of active metabolites and a limited propensity to drug-drug interactions. No clinically relevant changes in pharmacokinetic parameters were observed in T2DM patients or in patients with mild/moderate renal or hepatic impairment. Adverse events are a slightly increased incidence of mycotic genital and rare benign urinary infections. SGLT2 inhibitors have the potential to reduce several cardiovascular risk factors, and cardiovascular outcome trials are currently ongoing. The best positioning of SGLT2 inhibitors in the armamentarium for treating T2DM is still a matter of debate. [less ▲]

Detailed reference viewed: 18 (1 ULg)
Full Text
Peer Reviewed
See detailPharmacokinetic and toxicological considerations for the treatment of diabetes in patients with liver disease.
Scheen, André ULg

in Expert opinion on drug metabolism & toxicology (2014)

Introduction: Patients with type 2 diabetes have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis and about one-third of cirrhotic patients ... [more ▼]

Introduction: Patients with type 2 diabetes have an increased risk of chronic liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis and about one-third of cirrhotic patients have diabetes. However, the use of several antidiabetic agents may be a cause for concern in the case of hepatic impairment (HI). Areas covered: An extensive literature search was performed to analyze the influence of HI on the pharmacokinetics (PK) of glucose-lowering agents and the potential consequences for clinical practice as far as the efficacy/safety balance of their use in diabetic patients with CLD is concerned. Expert opinion: Almost no PK studies have been published regarding metformin, sulfonylureas, thiazolidinediones and alpha-glucosidase inhibitors in patients with HI. Only mild changes in PK of glinides, dipeptidyl peptidase-4 inhibitors and sodium glucose cotransporters type 2 inhibitors were observed in dedicated PK studies in patients with various degrees of HI, presumably without major clinical relevance although large clinical experience is lacking. Glucagon-like peptide-1 receptor agonists have a renal excretion rather than liver metabolism. Rare anecdotal case reports of hepatotoxicity have been described with various glucose-lowering agents contrasting with numerous reassuring data. Nevertheless, caution should be recommended, especially in patients with advanced cirrhosis, including with the use of metformin. [less ▲]

Detailed reference viewed: 3 (0 ULg)
Full Text
Peer Reviewed
See detailLinagliptin plus metformin: a pharmacokinetic and pharmacodynamic evaluation.
SCHEEN, André ULg

in Expert Opinion on Drug Metabolism & Toxicology (2013), 9(3), 363-77

INTRODUCTION: The first-choice drug therapy in the management of type 2 diabetes is metformin . However, most patients require a combined therapy to reach and/or maintain targets of glucose control ... [more ▼]

INTRODUCTION: The first-choice drug therapy in the management of type 2 diabetes is metformin . However, most patients require a combined therapy to reach and/or maintain targets of glucose control. Dipeptidyl peptidase-4 (DPP-4) inhibitors, commonly referred to as gliptins, offer new options for combined therapy with metformin. Linagliptin is the most recently launched gliptin, with a unique pharmacokinetic (PK) profile characterized by negligible renal excretion and is now also available as a fixed-dose combination (FDC) with metformin. AREAS COVERED: An extensive literature search was performed to analyze the potential PK and pharmacodynamic interactions between linagliptin and metformin. Linagliptin and metformin may be administered together, either separately or as FDC supported by bioequivalence studies. Linagliptin and metformin are not prone to PK drug-drug interactions. Their coadministration improves blood glucose control more potently than either compound separately, without hypoglycemia and without increasing metformin-related gastrointestinal side effects. EXPERT OPINION: The combination linaglitpin plus metformin, if not contraindicated (renal failure), may be used as first-line or second-line therapy in the management of type 2 diabetes. That being said, the durability of the glucose-lowering effect of this combination needs to be further explored in long-term controlled trials. [less ▲]

Detailed reference viewed: 21 (0 ULg)
Full Text
Peer Reviewed
See detailPharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease.
SCHEEN, André ULg

in Expert Opinion on Drug Metabolism & Toxicology (2013)

Introduction: People with chronic kidney disease (CKD) of stages 3 - 5 (creatinine clearance < 60 ml/min) represent approximately 25% of patients with type 2 diabetes mellitus (T2DM), but the problem is ... [more ▼]

Introduction: People with chronic kidney disease (CKD) of stages 3 - 5 (creatinine clearance < 60 ml/min) represent approximately 25% of patients with type 2 diabetes mellitus (T2DM), but the problem is underrecognized or neglected in clinical practice. However, most oral antidiabetic agents have limitations in case of renal impairment (RI), either because they require a dose adjustment or because they are contraindicated for safety reasons. Areas covered: The author performed an extensive literature search to analyze the influence of RI on the pharmacokinetics (PK) of glucose-lowering agents and the potential consequences for clinical practice. Expert opinion: As a result of PK interferences and for safety reasons, the daily dose should be reduced according to glomerular filtration rate (GFR) or even the drug is contraindicated in presence of severe CKD. This is the case for metformin (risk of lactic acidosis) and for many sulfonylureas (risk of hypoglycemia). At present, however, the exact GFR cutoff for metformin use is controversial. New antidiabetic agents are better tolerated in case of CKD, although clinical experience remains quite limited for most of them. The dose of DPP-4 inhibitors should be reduced (except for linagliptin), whereas both the efficacy and safety of SGLT2 inhibitors are questionable in presence of CKD. [less ▲]

Detailed reference viewed: 22 (3 ULg)
Full Text
Peer Reviewed
See detailSaxagliptin plus metformin combination in patients with type 2 diabetes and renal impairment.
SCHEEN, André ULg

in Expert Opinion on Drug Metabolism & Toxicology (2012), 8(3), 383-94

INTRODUCTION: A metformin plus saxagliptin fixed-dose combination is now proposed to clinicians. Furthermore, saxagliptin's license was recently extended to include diabetic patients with moderate or ... [more ▼]

INTRODUCTION: A metformin plus saxagliptin fixed-dose combination is now proposed to clinicians. Furthermore, saxagliptin's license was recently extended to include diabetic patients with moderate or severe renal impairment (RI). However, metformin is still contraindicated in patients with RI. AREAS COVERED: This review analyses the pro and contra of using a combination of saxagliptin and metformin (separately or as a fixed-dose combination) in type 2 diabetic patients with moderate or severe RI. An extensive literature search of all pharmacokinetic data and efficacy/safety profile of metformin and saxagliptin in subjects with RI was performed. EXPERT OPINION: Since both metformin and saxagliptin are excreted via the kidney, dose adjustment is required in case of moderate-to-severe RI (half dose of saxagliptin). However, major discrepancies exist between guidelines (metformin excluded in case of RI because of the risk of lactic acidosis) and real life (metformin widely prescribed in patients with some degree of RI). Physicians should weigh the benefit/risk ratio carefully before deciding to prescribe or withdraw the combination metformin plus saxagliptin in patients with stable RI. A redefinition of contraindications to metformin will enable more physicians to prescribe within guidelines and to administer saxagliptin combined with metformin in more patients who clearly may benefit from this combination. [less ▲]

Detailed reference viewed: 25 (2 ULg)
Full Text
Peer Reviewed
See detailPharmacokinetic evaluation of atorvastatin and sitagliptin in combination for the treatment of type 2 diabetes.
SCHEEN, André ULg

in Expert Opinion on Drug Metabolism & Toxicology (2012), 8(6), 745-58

INTRODUCTION: Patients with type 2 diabetes (T2DM) are exposed to a high risk of cardiovascular disease (CVD) requiring a global therapeutic approach. Statin therapy has proven its efficacy in reducing ... [more ▼]

INTRODUCTION: Patients with type 2 diabetes (T2DM) are exposed to a high risk of cardiovascular disease (CVD) requiring a global therapeutic approach. Statin therapy has proven its efficacy in reducing CVD events in T2DM patients. Dipeptidylpeptidase-4 inhibitors (gliptins), which are increasingly used to target hyperglycemia, also offer promising preliminary results regarding a possible reduction in CVD events. As most patients with T2DM may be treated with both a statin and a gliptin, dual pharmacological therapy, possibly as a fixed-dose combination (FDC), deserves further consideration. AREAS COVERED: The reader is provided with an update of information on the pharmacokinetics (PK) and pharmacodynamics (PD) of atorvastatin and sitagliptin . The article provides an analysis of the potential PK/PD interactions between the two compounds and puts into perspective the potential cardiovascular protection that such a dual therapy may offer in patients with T2DM. EXPERT OPINION: Atorvastatin and sitagliptin are not prone to PK drug-drug interactions. Their coadministration, either separately or in an FDC, improves both blood glucose levels and cholesterol concentrations, without clinically relevant adverse events. The atorvastatin plus sitagliptin combination may be used to reduce LDL cholesterol and hyperglycemia in patients with T2DM, with the aim to improve CVD prognosis and adherence to therapy. [less ▲]

Detailed reference viewed: 18 (0 ULg)
Full Text
Peer Reviewed
See detailLinagliptin for the treatment of type 2 diabetes (pharmacokinetic evaluation).
SCHEEN, André ULg

in Expert Opinion on Drug Metabolism & Toxicology (2011), 7(12), 1561-76

Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes (T2DM). The novel compound linagliptin has important different pharmacokinetic (PK ... [more ▼]

Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes (T2DM). The novel compound linagliptin has important different pharmacokinetic (PK) properties, when compared with previously commercialized DPP-4 inhibitors, which may offer some advantages in clinical practice. Linagliptin has a unique PK/pharmacodynamic (PD) profile and is the first DPP-4 inhibitor with a nonrenal elimination route. Therefore, it can be administered in patients with renal impairment without dose adjustment or monitoring of renal function. The drug has a low potential for drug-drug interactions (DDIs) and no clinically relevant ones were reported so far. Areas covered: An extensive literature search was performed to analyse primarily PK and secondarily PD characteristics of linagliptin in both healthy volunteers and patients with T2DM (treated with linagliptin as monotherapy or combined therapy). Updated information about linagliptin PK either after single administration (large dose range) or after chronic administration (steady state) were also included. A special focus has been put on DDIs and on PK/PD of linagliptin in patients with renal impairment. Expert opinion: Head-to-head comparative studies and/or increased clinical experience with DPP-4 inhibitors will determine the clinical advantage, if any, of one agent over another. [less ▲]

Detailed reference viewed: 25 (3 ULg)
Full Text
Peer Reviewed
See detailCytochrome P450-mediated cardiovascular drug interactions.
SCHEEN, André ULg

in Expert opinion on drug metabolism & toxicology (2011), 7(9), 1065-82

Introduction: There are numerous drug-drug interactions (DDIs) related to cardiovascular medications and many of these are mediated via the cytochrome P450 (CYP) system. Some of these may lead to serious ... [more ▼]

Introduction: There are numerous drug-drug interactions (DDIs) related to cardiovascular medications and many of these are mediated via the cytochrome P450 (CYP) system. Some of these may lead to serious adverse events and it is, therefore, essential that clinicians are aware of the important interactions that occur. Areas covered: An extensive literature search was performed to analyze the CYP-mediated cardiovascular DDIs that lead to a loss of efficacy or potential toxicity. Cardiovascular drugs may be victims or act as perpetrators of DDIs. The paper analyzes CYP-mediated drug interactions concerning anticoagulants, antiplatelet agents, antiarrhythmics, beta-blockers, calcium antagonists, antihypertensive medications, lipid-lowering drugs and oral antidiabetic agents. Expert opinion: Cardiovascular DDIs involving the CYP system are numerous. Additionally, the spectrum of drugs prescribed is constantly changing, particularly with cardiovascular diseases and it is not necessarily the case that drugs that had shown safety earlier will always show safety. Clinicians are encouraged to develop their knowledge of CYP-mediated DDIs so that they can choose safe drug combination regimens, adjust drug dosages appropriately and conduct therapeutic drug monitoring for drugs with narrow therapeutic indices. [less ▲]

Detailed reference viewed: 29 (6 ULg)
Full Text
Peer Reviewed
See detailPharmacokinetic and pharmacodynamic evaluation of sitagliptin plus metformin.
Scheen, André ULg

in Expert Opinion on Drug Metabolism & Toxicology (2010), 6(10), 1265-76

IMPORTANCE OF THE FIELD: Type 2 diabetes is an increasingly prevalent disease resulting from various complex combinations of defects in insulin secretion and insulin action. Adequate blood glucose control ... [more ▼]

IMPORTANCE OF THE FIELD: Type 2 diabetes is an increasingly prevalent disease resulting from various complex combinations of defects in insulin secretion and insulin action. Adequate blood glucose control is necessary to minimize complications. DPP IV inhibitors (sitagliptin, vildagliptin, saxagliptin) offer new options for combined pharmacological therapy. AREAS COVERED IN THIS REVIEW: An extensive literature search was performed to analyze the potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between metformin (first-line drug for the management of type 2 diabetes) and sitagliptin (first commercialized DPP IV inhibitor). Metformin and sitagliptin may be administered together, either separately or in fixed-dose combination. WHAT THE READER WILL GAIN: Updated information about PK/PD data on metformin alone, sitagliptin alone and sitagliptin plus metformin. Metformin and sitagliptin are not prone to PK drug-drug interactions. Their co-administration, either separately or in a fixed-dose combination, improves blood glucose control more potently than either compound separately, without hypoglycemia and without increasing metformin-related gastrointestinal side effects. TAKE HOME MESSAGE: The combination sitagliptin plus metformin may be used as a first- or second-line therapy in the management of type 2 diabetes. [less ▲]

Detailed reference viewed: 54 (2 ULg)
Full Text
Peer Reviewed
See detailSpotlight on adapalene.
Pierard, Gérald ULg; Franchimont, Claudine ULg; Paquet, Philippe ULg et al

in Expert opinion on drug metabolism & toxicology (2009), 5(12), 1565-75

BACKGROUND: In the field of dermatology, topical retinoids represent a mainstay in acne treatment. Adapalene is a naphthoic acid derivative showing some pharmacological activities similar to the regular ... [more ▼]

BACKGROUND: In the field of dermatology, topical retinoids represent a mainstay in acne treatment. Adapalene is a naphthoic acid derivative showing some pharmacological activities similar to the regular retinoids. The drug is used singly or in combination for treating acne and a few other miscellaneous skin disorders. OBJECTIVE: To critically review the pharmacokinetic, pharmacologic aspects and clinical benefits and adverse effects associated with topical adapalene. METHOD: A systematic literature review was conducted primarily based on PubMed citations. RESULTS/CONCLUSIONS: Adapalene shares some biological activities in common with retinoic acid. However, it exhibits distinct physicochemical and binding properties for selective retinoic acid receptors. In acne, adapalene is expected to reduce comedogenesis, expel mature comedones and exert some anti-inflammatory effects. The drug is effective as monotherapy in mild comedonal acne and in combination with benzoyl peroxide for mild-to-moderate inflammatory acne. The safety profile of adapalene is good. Indeed, only discrete to moderate adverse events including erytheme, xerosis, itching and stinging may develop during the early treatment phase. Clinical experience has established that adapalene represents a valuable addition to the other current treatments for acne. [less ▲]

Detailed reference viewed: 35 (3 ULg)
Full Text
Peer Reviewed
See detailIbandronate in profile: drug characteristics and clinical efficacy.
Reginster, Jean-Yves ULg; Neuprez, Audrey; Bruyère, Olivier ULg

in Expert Opinion on Drug Metabolism & Toxicology (2008), 4(7), 941-51

BACKGROUND: Postmenopausal osteoporosis is a serious, chronic condition, for which nitrogen-containing bisphosphonates are now one of the treatments of choice. OBJECTIVE: To review the profile of ... [more ▼]

BACKGROUND: Postmenopausal osteoporosis is a serious, chronic condition, for which nitrogen-containing bisphosphonates are now one of the treatments of choice. OBJECTIVE: To review the profile of ibandronate, a monthly oral (150 mg) or quarterly intravenous injection (3 mg) of bisphosphonate. METHODS: The literature search was limited to publications of ibandronate data. RESULTS/CONCLUSION: Ibandronate is rapidly absorbed and distributed in the bone; it is not metabolised and is excreted in urine. Clinical trial data have demonstrated the efficacy of ibandronate in reducing fracture risk, increasing bone mineral density and reducing bone turnover. These data are supported by recent meta-analyses and a large database study that have demonstrated antifracture efficacy with the ibandronate regimens used in clinical practice. Overall, ibandronate has generally been well tolerated. Therefore, ibandronate is a useful treatment for postmenopausal osteoporosis. [less ▲]

Detailed reference viewed: 36 (4 ULg)