Serum triamcinolone levels during intensive, inpatient wet-dressing therapy.

BACKGROUND: Wet dressings combined with topical corticosteroids are beneficial for patients with generalized and refractory dermatosis; however, to our knowledge, serum levels after topical corticosteroid absorption during intensive therapy have not been reported previously. AIM: To examine serum levels of triamcinolone acetonide (TAC) after topical corticosteroid application during intensive wet-dressing therapy. METHODS: We performed a retrospective study of adult patients admitted for inpatient wet-dressing therapy from 7 November 2015 to 24 June 2016. Data were collected on sex, age, body surface area, TAC serum levels, number of wet-dressing changes after 24 and 48 h, and type of wet dressing. RESULTS: In total, 29 patients (14 men, 15 women) were assessed. Median [interquartile range (IQR)] age was 57 years (51.5-67.0 years) and involved body surface area was 1.98 m2 (1.88-2.15) m2 . Before the 24-hour blood draw, patients had received 1-3 dressing changes. Median (IQR) TAC level at 24 h was 0.33 µg/dL (0.20-0.58 µg/dL), with no significant difference noted between the number of dressing changes and TAC serum level. At 48 h, results of a serum TAC test were available for 22 patients with 2-6 dressing changes. Mean (IQR) serum level was 0.30 µg/dL (0.30-0.87 µg/dL). For each additional dressing change, there was an estimated 0.21 µg/dL increase in TAC serum level (95% CI 0.11-0.31; P < 0.001). TAC serum level was not significantly associated with sex, age, body surface area or dressing type. CONCLUSIONS: Intensive, inpatient wet-dressing therapy is associated with detectable TAC serum levels. However, we suspect that topical TAC has a primarily local therapeutic effect on the skin.

Development and validation of a LC-MS/MS method for simultaneous determination of six glucocorticoids and its application to a pharmacokinetic study in nude mice.

In this study, a simple, rapid and sensitive LC-MS/MS analytical method for simultaneous determination of six glucocorticoids including 21-hydroxy deflazacort (21-OH DFZ), prednisolone (PNL), betamethasone (BET), beclomethasone (BEC), triamcinolone acetonide (TCA), budesonide (BUD) in nude mice plasma was developed and validated. Using testosterone as internal standard, the plasma samples were prepared by precipitation with acetonitrile and separated using an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm) with a mobile phase composed of acetonitrile and 0.1 % (v/v) formic acid aqueous solution by gradient elution at a flow rate of 0.3 mL/min. Quantitation was performed on a triple quadruple tandem mass spectrometer by multiple reaction monitoring in positive electrospray ionization mode. Calibration curves were developed over the range of 1-400 ng/mL for TCA, 5-2000 ng/mL for 21-OH DFZ, BET, BEC as well as BUD, and 10-2000 ng/mL for PNL. The accuracy, precision, matrix effect, recovery and stability were validated to be within acceptable criteria. The method was successfully applied to a preclinical pharmacokinetic (PK) study of the six GCs on female nude mice after a single oral dose of 1 mg/kg. The PK profiles of all the six GCs were described by two-compartment model with first-order absorption rate.

Elimination profile of triamcinolone hexacetonide and its metabolites in human urine and plasma after a single intra-articular administration.

Triamcinolone hexacetonide (THA) is a synthetic glucocorticoid (GC) used by intra-articular (IA) administration. GCs are prohibited in sports competitions by systemic routes, and they are allowed by other routes considered of local action (IA administration, among others). The aim of the present work was to study the metabolic profile of THA in urine and plasma following IA administration. Eight patients (4 males and 4 females) with knee osteoarthritis received an IA dose of THA (40 mg) in the knee joint. Spot urine and plasma samples were collected before injection and at different time periods up to day 23 and 10 post-administration, respectively. The samples were analysed by liquid chromatography-tandem mass spectrometry. Neither THA nor specific THA metabolites were detected in urine. Triamcinolone acetonide (TA) and 6ß-hydroxy-triamcinolone acetonide were the main urinary metabolites. Maximum concentrations wereobtained between 24 and 48 h after administration. Using the reporting level of 30 ng/mL to distinguish allowed from forbidden administrations of GCs, a large number of false adverse analytical findings would be reported up to day 4. On the other hand, TA was detected in all plasma samples collected up to day 10 after administration. THA was also detected in plasma but at lower concentrations. The detection of plasma THA would be an unequivocal proof to demonstrate IA use of THA. A reversible decrease was observed in plasma concentrations of cortisol in some of the patients, indicating a systemic effect of the drug.

Simultaneous determination of triamcinolone hexacetonide and triamcinolone acetonide in rabbit plasma using a highly sensitive and selective UPLC-MS/MS method.

An ultra-high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was successfully developed and qualified for the simultaneous determination of triamcinolone hexacetonide (TAH) and triamcinolone acetonide (TAA, the active metabolite of TAH) in rabbit plasma. To prevent the hydrolysis of TAH to TAA ex vivo during sample collection and processing, we evaluated the effectiveness of several esterase inhibitors to stabilize TAH in plasma. Phenylmethanesulfonyl fluoride (PMSF) at 2.0 mM was chosen to stabilize TAH in rabbit plasma. The developed method is highly sensitive with a lower limit of quantitation of 10.0 pg/mL for both TAA and TAH using a 300 µL plasma aliquot. The method demonstrated good linearity, accuracy, precision, sensitivity, selectivity, recovery, matrix effects, dilution integrity, carryover, and stability. Linearity was obtained over the range of 10-2500 pg/mL. Both intra- and inter-run coefficients of variation were less than 9.1% and accuracies across the assay range were all within 100 ±â€¯8.4%. The run time is under 5 minutes. The method was successfully implemented to support a rabbit pharmacokinetic study of TAH and TAA following a single intra-articular administration of TAH (Aristospan®).

Corticosteroid and Cortisol Serum Levels Following Intra-articular Triamcinolone Acetonide Lumbar Facet Joint Injections.

BACKGROUND: Facet joint steroid injections are used to treat chronic low back pain. However, little is known about the systemic absorption and serum levels of steroids following intra-articular facet joint injections. The primary objective of this preliminary study was to investigate the pharmacokinetics of triamcinolone acetonide following fluoroscopically guided intra-articular lumbar facet joint injections in a cohort of patients with chronic low back pain. A secondary aim was to investigate the effects of triamcinolone on serum cortisol levels following lumbar facet joint injections. METHODS: The study cohort included 5 patients undergoing fluoroscopically guided intra-articular lumbar facet joint injections at a pain medicine specialty clinic. Blood was collected prior to the injections and on days 1, 2, 4, 6, 8, 14, 21, 28, 35, and 42 following the injections. RESULTS: The terminal elimination half-life of triamcinolone in a noncompartmental analysis was 213 hours. The peak median triamcinolone concentration of 3.6 ng/mL was detected within 24 hours after the injections. Serum cortisol levels were < 30 ng/mL for an average of 4.4 days. The maximum effect of triamcinolone on cortisol suppression was observed with triamcinolone serum levels of > 1.9 ng/mL. CONCLUSIONS: The peak serum concentration of triamcinolone following intra-articular facet joint injections occurred within 24 hours. The median terminal elimination half-life was 213 hours, but baseline cortisol levels were suppressed for an average of 4.4 days. Clinically, the prolonged half-life and endocrine effects of triamcinolone could increase the risk for serious drug-drug interactions in patients taking medications that inhibit corticosteroid metabolism.

A randomized, controlled trial comparing topical steroid application to wet versus dry skin in children with atopic dermatitis (AD).

BACKGROUND: Soak and smear (SS), a technique whereby a bath is followed by topical corticosteroid (TCS) application to wet skin, is reported to be a beneficial adjunctive therapy for patients with recalcitrant atopic dermatitis (AD). OBJECTIVE: We evaluated whether SS is of greater benefit than application of TCS to dry skin for the treatment of childhood AD. METHODS: A randomized, investigator-blinded, controlled study was performed in children with AD. Patients were randomized to apply TCS either via SS (n = 22) or to dry skin (n = 23) for 14 days. The primary outcome was an improvement in the Eczema Area and Severity Index score. Secondary outcomes included assessments of disease burden, pruritus, and sleep; morning cortisol levels; and adverse effects. RESULTS: Patients with AD severity who applied TCS via SS or to dry skin improved 84.8% (95% confidence interval 77.5-92.1) and 81.4% (95% confidence interval 70.3-92.4) by Eczema Area and Severity Index score, respectively. There was no statistical difference between the 2 groups (P value = .85). LIMITATIONS: Small sample size limited the power of our study. CONCLUSIONS: We did not find that application of TCS to presoaked skin works better than application to dry skin for the treatment of AD in children.

Serum Triamcinolone Levels Following Interlaminar Epidural Injection.

BACKGROUND: Lumbar interlaminar epidural steroid injections (ESIs) are one of the most commonly performed procedures in pain medicine, but little is known about the serum levels of steroids following injection into the epidural space. The primary objective of this study was to investigate the pharmacokinetics of fluoroscopy-guided epidural-administered triamcinolone acetonide in a cohort of patients with chronic low-back pain seeking treatment in a pain medicine clinic. METHODS: The study cohort included 10 patients undergoing a fluoroscopically guided L4-L5 or L5-S1 lumbar interlaminar ESI at a pain medicine specialty clinic. Blood was collected prior to the ESI and on days 1, 2, 4, 6, 8, 14, 21, 28, 35, and 42 following the injection. The sample extract was analyzed by tandem mass spectrometry. RESULTS: The terminal elimination half-life of epidural-administered triamcinolone in a noncompartmental analysis was 523 hours. In the noncompartmental analysis, peak triamcinolone concentrations of 4.1 ng/mL were detected within 24 hours after administration. CONCLUSIONS: The pharmacokinetics of epidural-administered triamcinolone is consistent with previously observed adverse effects of the drug on endocrine function. The pharmacokinetics of other epidural-administered steroids should be determined and incorporated in clinical trials to investigate the potential associations between serum levels, clinical outcomes, and potential adverse endocrine effects.

Simultaneous determination of triamcinolone acetonide palmitate and triamcinolone acetonide in beagle dog plasma by UPLC-MS/MS and its application to a long-term pharmacokinetic study of triamcinolone acetonide palmitate lipid emulsion injection.

In order to investigate the pharmacokinetics of triamcinolone acetonide palmitate (TAP) which is a lipid-soluble prodrug of triamcinolone acetonide (TA), a rapid, simple, sensitive and reproducible UPLC-MS/MS method has been developed and validated for the simultaneous determination of TAP and TA in beagle dog plasma. After simple liquid-liquid extraction, the analytes and internal standard (dexamethasone, DEX) were separated on Phenomenex Luna C18 column (50 mm × 2.1mm, 1.7 µm) using a mobile phase consisting of solvent A (acetonitrile) and solvent B (0.1% ammonia solution) at a flow rate of 0.2 ml/min with gradient elution. Acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM) mode via positive electrospray ionization using the ion transitions of m/z 673.5→397.3, 435.3→415.3 and 393.3→355.3 for TAP, TA and IS, respectively. The method was of satisfactory specificity, sensitivity, precision and accuracy over the concentration range of 1-1,000 ng/ml for TAP and 0.5-500 ng/ml for TA. The intra- and inter-day precisions for both TAP and TA were 3.2% to 18.7% and the accuracy was in the range of -8.4% to 6.8%. The mean recoveries of TAP, TA and IS were 86.7-104.7%. The method was successfully applied to a long-term pharmacokinetic study of TAP and TA after 28-day repeated intravenous administration of TAP lipid emulsion injection to beagle dogs.

Inhibitory effect of triamcinolone acetonide on synthesis of inflammatory mediators in the equine.

Glucocorticoids (corticosteroids) are widely used anti-inflammatory agents in veterinary medical practice. These drugs are considered doping agents because they mask pain and thus, increase injury potential in equine athletes. They exhibit anti-inflammatory property by binding to glucocorticoids receptor (GR) to control the transcription of pro- and anti-inflammatory cytokines and enzymes involved in the synthesis of bioactive eicosanoids. To evaluate the role of triamcinolone acetonide (TA) on concentrations of bioactive eicosanoids in equine plasma, TA (0.04 mg/kg) was intravenously administered to horses. Before (0 h) and after TA administration, equine whole blood (EWB) samples were collected and challenged with either methanol (vehicle), calcium ionophore A-23187 (CI) or lipopolysaccharide (LPS) to stimulate ex-vivo synthesis of eicosanoids. Plasma concentrations of eicosanoids were quantified using LC-MS/MRM. Results showed that thromboxane B2 (TXB2) was not affected by TA administration when EWB was stimulated with CI. However, after LPS treatment, TXB2, PGE2, PGF2α and 15-(s)-HETE decreased during 2-8 h post-TA administration but recovered to concentrations which were not significantly different from those of pre-TA administration (0 h), after 24 h. When EWB was treated with CI, LTB4 was suppressed post-TA administration compared to 0 h. When EWB collected after TA administration was stimulated with LPS, LTB4 was not significantly different from those of 0 h. Administration of a therapeutic dose of TA (0.04 mg/kg, iv) in the horse suppressed biosynthesis of bioactive eicosanoids indicating the anti-inflammatory role of TA in the horse.

Pharmacokinetics of triamcinolone acetonide following intramuscular and intra-articular administration to exercised Thoroughbred horses.

REASON FOR PERFORMING STUDY: The use of triamcinolone acetonide (TA) in performance horses necessitates establishing appropriate withdrawal times prior to performance. OBJECTIVES: To describe the plasma pharmacokinetics of TA and time-related urine and synovial fluid concentrations following i.m. and intra-articular administration to exercised Thoroughbred horses. STUDY DESIGN: Block design. METHODS: Twelve racing fit adult Thoroughbred horses received a single i.m. administration of TA (0.1 mg/kg bwt). After an appropriate washout period, the same horses then received a single intra-articular TA administration (9 mg) into the right antebrachiocarpal joint. Blood, urine and synovial fluid samples were collected prior to, and at various times, up to 60 days post drug administration and analysed using liquid chromatography-mass spectrometry. Plasma data were analysed using noncompartmental analysis. RESULTS: Maximum measured plasma TA concentrations were 0.996 ± 0.391 at 13.2 h and 1.27 ± 0.278 ng/ml at 6.5 h for i.m. and intra-articular administration, respectively. The plasma terminal elimination half-life was 11.4 ± 6.53 and 0.78 ± 1.00 days for i.m. and intra-articular administration, respectively. Following i.m. administration, TA was below the limit of detection (LOD) by Days 52 and 60 in plasma and urine, respectively. Following intra-articular administration TA was undetectable by Day 7 in plasma and Day 8 in urine. Triamcinolone acetonide was also undetectable in any of the joints sampled following i.m. administration and remained above the limit of quantitation (LOQ) for 21 days following intra-articular administration. CONCLUSIONS AND POTENTIAL RELEVANCE: This study extends previous studies describing the pharmacokinetics of TA following i.m. and intra-articular administration to the horse and suggests that plasma and urine concentrations are not a good indicator of synovial fluid concentrations. Furthermore, results of this study supports an extended withdrawal time for TA given i.m.

[Determination of mitomycin C in rabbit plasma by ultra-high performance liquid chromatography-tandem mass spectrometry].

An ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of mitomycin C (MMC) in rabbit plasma was established. The blank rabbit plasma sample solutions added with mitomycin C and triamcinolone acetonide (internal standard, IS) were prepared. The solutions containing MMC and IS were extracted from the plasma with ethyl acetate using liquid-liquid extraction method. A Hypersil Gold C18 column (50 mm x 2.1 mm, 1.9 microm) was employed and the column temperature was set at 35 degrees C. The isocratic elution of methanol and 0.1% (v/v) formic acid aqueous solution as mobile phase was performed at a flow rate of 0.2 mL/min, and a rapid separation was completed within 3 min. The electrospray was operated in the positive ionization mode and the MMC and IS were identified in selected reaction monitoring (SRM) mode. The monitoring ions of MMC and IS were m/z 335. 2 --> 242.2 and m/z 435.2 --> 397. 3/415.2, respectively, which were used to qualify and quantify the targets by the method of matrix-matched standard solution. The calibration curve showed good linearity within the mass concentrations of 1 to 1 000 microg/L (r = 0.997 8, weighting: 1/x2). The limit of detection (S/N = 3) was 0.2 microg/L. The recoveries were from 85% to 115% at the spiked levels of 1, 5, 100 and 800 microg/L, and the relative standard deviations (RSDs) of intra- and inter-day were both less than 15%. The method can meet the determination requirements of biological samples, and can be used for the determination of mitomycin C in rabbit plasma after the administration of mitomycin C. The method is selective, sensitive, convenient, rapid and reproducible in the determination of mitomycin C, and also can be used for the pharmacokinetics research of mitomycin C in plasma.

Pharmacokinetics of intra-articular, intravenous, and intramuscular administration of triamcinolone acetonide and its effect on endogenous plasma hydrocortisone and cortisone concentrations in horses.

OBJECTIVE: To compare pharmacokinetics of triamcinolone acetonide (TA) following i.v., intra-articular (i.a.), and i.m. administration and determine its effect on plasma concentrations of hydrocortisone and cortisone. ANIMALS: 6 Thoroughbreds. PROCEDURES: TA (0.04 mg/kg) was administered i.v., i.m., or i.a., and plasma TA, hydrocortisone, and cortisone concentrations were determined. RESULTS: I.v. administration of TA was fitted to a 2-compartment model. Median distribution half-life was 0.50 hours (range, 0.24 to 0.67 hours); elimination half-life was 6.1 hours (range, 5.0 to 6.4 hours). Transfer half-life of TA from joint to plasma was 5.2 hours (range, 0.49 to 73 hours); elimination half-life was 23.8 hours (range, 18.9 to 32.2 hours). Maximum plasma concentration following i.a. administration was 2.0 ng/mL (range, 0.94 to 2.5 ng/mL), and was attained at 10 hours (range, 8 to 12 hours). Maximum plasma concentration following i.m. administration was 0.34 ng/mL (range, 0.20 to 0.48 ng/mL) and was attained at 13.0 hours (range, 12 to 16 hours); concentration was still quantifiable at 360 hours. Hydrocortisone plasma concentrations were significantly different from baseline within 0.75, 2, and 1 hours after i.v., i.a., and i.m. administration, respectively, and remained significantly different from baseline at 96 and 264 hours for i.v. and i.a. administration. Following i.m. administration of TA, plasma concentrations of hydrocortisone did not recover to baseline concentrations by 360 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetics of TA and related changes in hydrocortisone were described following i.v., i.a., and i.m. administration. A single administration of TA has profound effects on secretion of endogenous hydrocortisone.

Simultaneous HPLC analysis of triamcinolone acetonide and budesonide in microdialysate and rat plasma: application to a pharmacokinetic study.

A specific and reliable HPLC-PDA method for the quantitative determination of triamcinolone acetonide, budesonide and fluticasone propionate (as internal standards) in small volumes of microdialysate and rat plasma was developed. An efficient solid-phase extraction (SPE) procedure for plasma samples yielded extremely clean extracts with overall recovery of 104.3% and 95.7% for triamcinolone acetonide (TA) and fluticasone propionate, respectively. Plasma extracts obtained after SPE and microdialysis samples were directly injected on a C18 column to separation. The method has been validated with good linearity, sensitivity, specificity and high accuracy (RE -5.28% to 9.14%) and precision (CV 0.50% to 6.62%) on both matrices. In stability studies, TA and budesonide were stable during storage and assay procedures. The method was applied to a pharmacokinetic study in rodents using microdialysis to determine protein unbound TA concentrations in blood and muscle.

Characterisation of systemic and ocular drug level of triamcinolone acetonide following a single sub-Tenon injection.

AIM To characterise the pharmacokinetics of triamcinolone acetonide (TA) in various ocular tissues following a single sub-Tenon injection. METHODS Twenty-one Chinchilla adult pigmented rabbits received sub-Tenon injection of TA (40 mg in 0.4 ml) in their right eyes. Three animals were killed at each designated time points (3 h, 1 day, 3 days, 7 days, 14 days, 21 days and 30 days) and the globes were snap frozen and dissected into aqueous, iris-ciliary body, vitreous, neuroretina and retinal pigment epithelium (RPE)/choroid. The concentrations of TA in the various ocular tissues were analysed using ultra-performance liquid chromatography, coupled with tandem mass spectrometric detection. RESULTS TA concentration followed a mono-exponential decrease over the study period in all ocular tissues of the injected eyes. The concentration was much higher in the RPE/choroid (892.14+/-558.11 ng/g at post-injection day 30) than in the other tissues (171.65+/-136.40 ng/g in neuroretina, 15.65+/-23.06 ng/ml in vitreous, 3.76+/-1.79 ng/g in iris-ciliary body, 2.64+/-0.96 ng/ml in aqueous at post-injection day 30). The TA level in the RPE/choroid had the lowest coefficient of logarithmic regression (0.07 in RPE/choroid, 0.10 in neuroretina, 0.11 in vitreous, 0.17 in iris-ciliary body, 0.18 in aqueous), indicating a 2.6 times slower clearance than in aqueous. The half-life of TA was 10.4 days in RPE/choroid. TA was detectable in the fellow eyes and was also detectable at very low levels in all blood samples during the entire study period. CONCLUSION TA was mostly cleared from RPE/choroid and retina in a mono-exponential mode. TA was above the therapeutic level for at least 30 days following a sub-Tenon injection.

Kaposi's sarcoma after long-acting steroids: time until remission and drug washout.

Long-acting steroids (LAS) are widely used to treat various inflammatory diseases and allergies. They have many adverse effects including the inhibition of the hypothalamopituitary axis that can last several months. LAS are also strong immunosuppressors and can result in severe opportunistic infections and immunodeficiency-related malignancies. However, the time needed for immune recovery after withdrawal of LAS is unknown. Here we report a case of Kaposi's sarcoma (KS) and severe immunosuppression after a chronic triamcinolone acetonide (TA) treatment. Six months after withdrawal, traces of TA were still detected in the serum by HPLC mass spectrometry. At 8 months, the drug became undetectable, and clinical and biological signs of immune recovery - beginning of KS regression, normalization of IgG levels and CD4 T lymphocyte counts - became noticeable. We then provide a review of the literature on the time until remission of KS after immunosuppression reduction. We also reviewed the cases of KS induced by TA, and the metabolic side effects of TA when compared to standard glucocorticoids.

Ultra-sensitive quantification of corticosteroids in plasma samples using selective solid-phase extraction and reversed-phase capillary high-performance liquid chromatography/tandem mass spectrometry.

Low-dose corticosteroids may provide a favorable benefit/risk ratio for many therapeutic applications. However, the extremely low plasma drug concentrations achieved, in conjunction with the insufficient sensitivity/ selectivity of current analytical methods, renders the evaluation of corticosteroid pharmacokinetics (PK) a significant challenge under such conditions. Furthermore, targeted therapeutic strategies involving administration by inhalation or intraocular injection could result in very low but sustained systemic corticosteroid concentrations, which must be quantified to determine potential side effects. Here we describe a robust method for the ultrasensitive quantification of corticosteroids in plasma samples. This was achieved by the combination of a selective solid-phase extraction (SPE) with a highly sensitive capillary LC (microLC)-MS/MS analysis. SPE washing and elution conditions were optimized so that target drugs are selectively extracted from plasma. By eliminating most undesirable compounds from the sample matrix, this selective SPE procedure enabled a high sample loading volume on the microLC column without compromising chromatographic performance and operational robustness and helped to achieve ultralow detection limits for the corticosteroids in plasma. The effect of microLC separation on the signal-to-noise ratio of corticosteroid peaks in plasma samples was investigated. It was found that with sufficient microLC separation, sensitivity was improved because of a decrease in matrix effects and the removal of endogenous interferences. Detection limits of four clinically important corticosteroids (budesonide, dexamethasone, triamcinolone acetonide, and dexamethasone acetate) ranged from 0.2 to 1 pg/mL in plasma, and linearity was good for all drugs in the range of 5-5000 pg/mL. Accuracy was 88-107% and the variation (CV%) was 2.3-11.1%. A limit of quantification (LOQ) of 5 pg/mL was validated for all four compounds. We applied this method to quantify the low levels of triamcinolone acetonide (TACA) in porcine plasma following suprachoroidal administration, which is necessary to estimate systemic drug exposure resulting from this novel clinical approach for treating inflammatory diseases of the eye. TACA in plasma could be quantified at low pg/mL levels for up to 90 days posttreatment. To our knowledge, this is the first practical analytical approach that can monitor plasma corticosteroids after intraocular administration, given the ultralow plasma concentrations achieved. In summary, this strategy enables PK analysis of corticosteroids in treatment regimens that result in extremely low systemic concentrations, and the approach can be extended for the sensitive quantification of other drugs.

Glucocorticoid resorption and influence on the hypothalamic-pituitary-adrenal axis after intra-articular treatment of the knee in resting and mobile patients.

BACKGROUND: Studies have shown that intra-articular glucocorticoid injection treatment for knee synovitis has a better outcome in resting patients than in mobile patients. One reason for this observation might be that rest retards steroid resorption, causing an enhanced local treatment effect. OBJECTIVES: To study drug resorption and the impact on hormone production in the hypothalamic-pituitary-adrenal axis after intra-articular glucocorticoid administration, with and without postinjection rest. METHODS: Twenty patients with rheumatoid arthritis and knee synovitis were randomised to either 24 hour bed rest or normal activity after intra-articular glucocorticoid treatment with 20 mg triamcinolone hexacetonide (THA). Serum levels of THA, cortisol, and adrenocorticotropic hormone (ACTH) were followed during 2 weeks. RESULTS: Short term and reversible decreases in serum cortisol and ACTH levels (p<0.001) were seen, without any significant differences between resting and mobile patients. The THA levels increased similarly in both groups, with the median serum peak seen after 8 hours. CONCLUSION: Immobilisation does not appear to retard glucocorticoid resorption after intra-articular administration. Further studies are therefore needed to clarify the mechanism behind the beneficial effects of rest after intra-articular glucocorticoid treatment for knee synovitis.

Cushing's syndrome after intra-articular and intradermal administration of triamcinolone acetonide in three pediatric patients.

BACKGROUND: Intra-articular and intradermal steroids are often used for their antiinflammatory effect. There is limited experience with intra-articular and intralesional administration of corticosteroids in the pediatric age group. DESIGN/METHODS: We performed a retrospective chart review of 3 pediatric patients who developed Cushing's syndrome after local administration of triamcinolone acetonide (TCA). RESULTS: Two females 9 and 17 years old, received intra-articular injections of TCA. One patient received multiple injections of TCA into the interphalangeal joints (cumulative dose: 120 mg), whereas the other received a single injection of 40 mg, a dose that is considered to be in the therapeutic range, into the hip joint. The third patient, a 7-year-old female, received multiple intralesional injections of TCA. These patients developed signs and symptoms of hypercortisolism that appeared 4 to 6 weeks after local administration of TCA and lasted for 4 to 6 months after the last dose of TCA. TCA was detectable in the plasma and urine by the liquid chromatography/tandem mass spectrometry method 4 to 5 months after the last dose of the steroid. CONCLUSIONS: We noted evidence for Cushing's syndrome in 3 pediatric patients after intra-articular or intradermal administration of TCA. One of them had received a therapeutic dose of TCA. The possibility of hypothalamic-pituitary-adrenal axis suppression should be considered in patients who have received intra-articular or intradermal steroid injections, particularly in those who have had multiple or relatively high doses.