Abstract:
:Sirolimus is a new immunosuppressive drug that has been evaluated in animal experiments. The current study was conducted on humans with reformulated sirolimus in doses from 3 mg/m2 to 15 mg/m2. Sixteen renal transplant recipients were included in this phase I study to determine the safety, tolerance, and preliminary pharmacokinetics of increasing single doses of orally administered sirolimus. All 16 patients had stable renal graft function after a renal transplant at least 6 months before the study. Basal immunosuppression consisted of cyclosporine and prednisolone (n = 10) or cyclosporine, azathioprine, and prednisolone (n = 6). Four groups (I, 3 mg/m2; II, 5 mg/m2; III, 10 mg/m2; IV, 15 mg/m2) of four patients were assigned randomly to receive sirolimus (n = 3) or placebo (n = 1). Among the 12 patients who received sirolimus, five had mild transient study events such as headache, nausea, mild dizziness, hypoglycemia, epistaxis, and decrease in platelets. No serious adverse events occurred and no nephrotoxic effects could be related to the single dose administration of sirolimus. The only study event that was judged as probably related to sirolimus was the single case of thrombocytopenia. The other events were evaluated as possibly related. Thrombocytopenia occurred at the highest dose level (15 mg/m2 sirolimus). In two of the patients in the placebo group, slight elevations of liver enzymes and serum amylase were seen. Blood and plasma sirolimus concentrations were analyzed by an electrospray-high performance liquid/mass spectrophotometric (ESP-HPLC/MS) method Sirolimus showed an extensive red blood cell distribution with a mean blood/ plasma ratio of 49.1. The elimination half-life ranged from 43.8 to 86.5 hours (mean 56.9 hours). The Cmax and the area under the concentration versus time curves (AUC) correlated reasonably with doses from 3 to 15 mg/m2. The oral dose clearance ranged from 42 to 339 ml/h.kg. No clinically significant differences were seen in the trough concentrations of cyclosporine or the AUCs before and after the administration of sirolimus. Administration of single oral doses of sirolimus from 3 to 15 mg/m2 was safe and well tolerated in stable renal transplant recipients. Thrombocytopenia may be the dose-limiting toxicity. Additional phase II and phase III clinical trials will define the immunosuppressive efficacy of sirolimus.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Brattström C,Säwe J,Tydén G,Herlenius G,Claesson K,Zimmerman J,Groth CGdoi
10.1097/00007691-199708000-00007subject
Has Abstractpub_date
1997-08-01 00:00:00pages
397-406issue
4eissn
0163-4356issn
1536-3694journal_volume
19pub_type
临床试验,杂志文章,随机对照试验abstract::Drug discovery programs are actively exploring for therapeutic agents targeting enzymes and receptors regulating sphingolipid metabolism and biologic functions. FTY720 is a close structural analogue of sphingosine with immunomodulatory properties. After oral administration, FTY720 is phosphorylated by sphingosine kina...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200412000-00001
更新日期:2004-12-01 00:00:00
abstract::Lidocaine is widely used in antiarrhythmic therapy, and the need to monitor the drug concentration in the blood of patients receiving lidocaine is well established. We have developed a new assay for lidocaine designed for the routine clinical therapeutic drug monitoring laboratory. A 100-microliter aliquot of blood pl...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198102000-00010
更新日期:1981-01-01 00:00:00
abstract:BACKGROUND:Previous reports have suggested that polymorphism of the opioid receptor A118G affects the efficacy of opioid analgesia. The aim of this study was to investigate whether such polymorphism contributed to variability in epidural mixture (sufentanil plus ropivacaine) requirements through patient-controlled epid...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000112
更新日期:2015-02-01 00:00:00
abstract::Steady-state serum concentrations of quetiapine were recorded in 62 psychiatric patients under routine conditions. Doses were administered twice daily, and serum quetiapine levels were measured in the morning about 12 hours after the last dose. Eight patients were in monotherapy, whereas the rest received various addi...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-200410000-00005
更新日期:2004-10-01 00:00:00
abstract::Eight commercial digoxin immunoassay methods were tested in 17 subjects taking spironolactone (but not digoxin) to evaluate cross-reactivity from parent drug and/or metabolites. Four of these methods showed significant (up to 1.9 nmol/L) and variable "apparent digoxin" concentrations, despite the absence of digoxin in...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198706000-00014
更新日期:1987-06-01 00:00:00
abstract::The concentration of haloperidol in hair was measured by radioimmunoassay after hairs were dissolved in 2.5 N NaOH solution and the drug was extracted. In patients to whom haloperidol had been administered at fixed daily doses for more than 1 month, and in whom therapy had been just discontinued (group A, n = 5) or th...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198911000-00013
更新日期:1989-11-01 00:00:00
abstract:BACKGROUND:Paclitaxel (PTX; Taxol, Abraxane) is used in many regimens for breast cancer, non-small cell lung cancer (NSCLC), and ovarian cancer. Multiple studies have demonstrated that PTX exhibits a greater than 10-fold interpatient variability of clearance rates when patients are dosed according to body surface area ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e318296be01
更新日期:2013-12-01 00:00:00
abstract::Digoxin and gentamicin are widely used in pediatric medicine, and therapeutic monitoring is mandatory because of their narrow margin of safety and wide interpatient and intrapatient pharmacokinetic variabilities. Saliva sampling may be of potential interest, especially in children, in whom blood sampling is often diff...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199806000-00003
更新日期:1998-06-01 00:00:00
abstract::The immunosuppressants cyclosporine, tacrolimus, sirolimus, everolimus, and probably also mycophenolic acid require therapeutic drug monitoring (TDM)-guided dosing to ensure that blood concentrations are kept within the target range in transplant patients. Reliable, accurate, and precise test methods are therefore ess...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000205
更新日期:2015-12-01 00:00:00
abstract::It is generally accepted that chemical testing of biologic fluids is the most objective means of diagnosis of drug use. The presence of a drug analyte in a biologic specimen can be used to document exposure. The standard for drug testing in toxicology is an immunoassay screen conducted on a urine sample, followed by c...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200204000-00006
更新日期:2002-04-01 00:00:00
abstract:BACKGROUND:The indication for the antiepileptic drug lacosamide (LCM) was recently extended to include children from the age of 4 years. Real-life data on the use and serum concentrations of LCM in children and adolescents are limited. The purpose of this study was to investigate the use of LCM in this patient group in...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000599
更新日期:2019-06-01 00:00:00
abstract::A gas chromatography-mass spectrometry (GC-MS)-based screening procedure was developed for the detection of diuretics, uricosurics, and/or their metabolites in human urine after extractive methylation. Phase-transfer catalyst remaining in the organic phase was removed by solid-phase extraction on a diol phase. The com...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000160719.96445.91
更新日期:2005-08-01 00:00:00
abstract::Major advances in immunosuppression and reductions in the rates of acute rejection have led to increasing graft and patient survival rates during the past two decades. Chronic dysfunction of the renal allograft, however, remains a major clinical problem and probably represents the end result of the complex interplay b...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200202000-00007
更新日期:2002-02-01 00:00:00
abstract::Twenty-five healthy volunteers were given 100 mg caffeine orally and several estimates of cytochrome P450 1A2 (CYP1A2) activity were evaluated. The validation was performed by correlation of different parameters in plasma, saliva, and urine to two measures of caffeine clearance, CL(oral) and CL(137X-->17X) that served...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200008000-00008
更新日期:2000-08-01 00:00:00
abstract::Plasma concentration-antidepressant response relationships for dothiepin, nordothiepin, dothiepin-S-oxide, and nordothiepin-S-oxide were investigated in 50 patients (33 women and 17 men), who had had a major depressive episode. Depression and anxiety were assessed at the start of therapy and after 2 and 4 weeks by mea...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-199310000-00001
更新日期:1993-10-01 00:00:00
abstract::Sixty-two serum samples from 28 pediatric epileptic patients under treatment with phenytoin [diphenylhydantoin (DPH)] were obtained to study the correlation between total and free serum DPH concentrations. The effect of coadministered antiepileptic drugs on DPH protein binding was also studied. Binding of DPH to serum...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::Two blood-sampling techniques, capillary and venous, were compared using the EMIT method. No difference was found in reproducibility. However, persistent positive bias of 0.628 micrograms/ml (p less than 0.01) was noted with the capillary sampling method. Any hemolysis that occurred in the capillary sampling technique...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198303000-00011
更新日期:1983-01-01 00:00:00
abstract::Plasma levels of haloperidol were monitored in children and teenagers suffering from psychotic episodes and/or abnormal movements (tics and Gilles de la Tourette's syndrome). Steady-state concentrations of haloperidol ranged from 0.7 to 19 ng/ml without any apparent relationship with the administered dose (15--285 mic...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-197901000-00004
更新日期:1979-01-01 00:00:00
abstract::This laboratory has developed a simple and efficient solid-phase extraction method that is combined with a high-performance liquid chromatographic method for rapid and precise therapeutic monitoring of haloperidol (Haldol) blood levels. The solid-phase extraction utilizes a mixed bed column. Sensitivity of the chromat...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199410000-00011
更新日期:1994-10-01 00:00:00
abstract::This study explored the association of 14 single nucleotide polymorphisms in three genes coding for influx transporters (SLC22A1, SLCO1B1, and SLCO1B3), two genes coding for efflux transporters (ABCB1 and ABCG2), and four genes coding for enzymes (CYP2C9, CYP2C19, CYP2D6, and CYP3A5) with the pharmacokinetics of imati...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31820beb02
更新日期:2011-04-01 00:00:00
abstract::An isocratic, high-performance liquid chromatography method has been developed for simultaneous determination of the oral antidiabetic tolbutamide and two of its metabolites, 4-hydroxytolbutamide and carboxytolbutamide, in human plasma and urine. The method was based on simple one-step liquid-liquid extraction with te...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199912000-00015
更新日期:1999-12-01 00:00:00
abstract::The high incidence of psychiatric illness in the postpartum period and the increasing percentage of women who breastfeed has focused attention on the treatment of breastfeeding women with psychotropic medications and, additionally, the exposure of nursing infants to these medications. Consequently, there has been an i...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200402000-00011
更新日期:2004-02-01 00:00:00
abstract:INTRODUCTION:Gabapentin (Neurontin) and levetiracetam (Keppra) are anticonvulsants with novel structures and suggested therapeutic ranges of 2-10 mg/L and 6-20 mg/L, respectively. Gabapentin is also used extensively to manage neuropathic pain, and for this indication, wherein higher doses are prescribed, plasma concent...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31820b1fce
更新日期:2011-04-01 00:00:00
abstract::The clinical usefulness of cyclosporine is hampered by dose-limiting toxicities to the kidney that are not predicted by drug levels in serum or whole blood. Because of its lipophilic nature, circulating plasma lipoproteins may play a role in drug disposition. This study characterized the pharmacokinetic parameters of ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199003000-00004
更新日期:1990-03-01 00:00:00
abstract::The objective of this study was to evaluate the analytical performance of the Abbott ARCHITECT Cyclosporine (CsA) immunoassay in 7 clinical laboratories in comparison to liquid chromatography/tandem mass spectrometry (LC/MS/MS), Abbott TDx, Cobas Integra 800, and the Dade Dimension Xpand immunoassay. The ARCHITECT ass...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,多中心研究
doi:10.1097/FTD.0b013e3181d46386
更新日期:2010-04-01 00:00:00
abstract::We report a clinically relevant suspected interaction between acyclovir and the antiepileptic drugs phenytoin (PHT) and valproic acid (VPA). In a child receiving PHT and VPA therapy, a 6-day acyclovir treatment reduced PHT and VPA plasma concentrations to subtherapeutic values. This probably worsened both clinical sta...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract:BACKGROUND:Therapeutic drug monitoring (TDM) involves the measurement of serum drug concentrations to optimize pharmacotherapy. Traditionally, blood pressure measurements alone, and not TDM, have been used to evaluate the antihypertensive drug response. However, approximately 50% of hypertensive patients treated with l...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000806
更新日期:2021-02-01 00:00:00
abstract::Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug resistant Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus. The adverse effects of linezolid can include thrombocytopenia and ne...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000710
更新日期:2020-02-01 00:00:00
abstract::Determination of plasma methadone is essential in connection with dose adjustments for patients participating in methadone maintenance programs. We successfully adapted the existing fluorescence polarization immunoassay (FPIA) kit intended for urinary methadone to plasma assays. A concentration interval of 50-900 ng/m...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
abstract::A population pharmacokinetic model was developed after administration of orogastric and/or intravenous indomethacin for the treatment of patent ductus arteriosus in preterm infants. Plasma indomethacin concentrations (n=227) were obtained from 90 preterm infants of median gestational age 27 weeks, mean postnatal age o...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/FTD.0b013e31815b3e13
更新日期:2007-12-01 00:00:00