OBJECTIVE To characterize pharmacokinetics of cyclophosphamide and 4-hydoxycyclophosphamide (4-OHCP) in the plasma of healthy cats after oral, IV, and IP administration of cyclophosphamide.
ANIMALS 6 healthy adult cats.
PROCEDURES Cats were randomly assigned to receive cyclophosphamide (200 mg/m2) via each of 3 routes of administration (oral, IV, and IP); there was a 30-day washout period between successive treatments. Plasma samples were obtained at various time points for up to 8 hours after administration. Samples were treated with semicarbazide hydrochloride to trap the 4-OHCP in stable form, which allowed for cyclophosphamide and trapped 4-OHCP to be simultaneously measured by use of tandem mass spectrometry. Pharmacokinetic parameters were determined from drug concentration-versus-time data for both cyclophosphamide and 4-OHCP.
RESULTS Cyclophosphamide was tolerated well regardless of route of administration. Pharmacokinetic parameters for 4-OHCP were similar after oral, IV, and IP administration. Area under the concentration-time curve for cyclophosphamide was lower after oral administration than after IV or IP administration.
CONCLUSIONS AND CLINICAL RELEVANCE Cyclophosphamide can be administered interchangeably to cats as oral, IV, and IP formulations, which should provide benefits with regard to cost and ease of administration to certain feline patients.
Objective—To determine the feasibility of the use of Fourier-transform infrared (FTIR) spectroscopy within the midinfrared range to differentiate synovial fluid samples of joints with osteochondrosis from those of control samples.
Animals—33 horses with osteochondrosis of the tarsocrural joint and 31 horses free of tarsocrural joint disease.
Procedures—FTIR spectroscopy of synovial fluid was used. Sixty-four synovial fluid samples from the tarsocrural joint were collected. Of these, 33 samples were from horses with radiographic evidence of osteochondrosis of the tarsocrural joint and 31 from control joints. Disease-associated features within infrared spectra of synovial fluid were statistically selected for spectral classification, and the variables identified were used in a classification model. Linear discriminant analysis and leave-one-out cross-validation were used to develop a classifier to identify joints with osteochondrosis.
Results—12 significant subregions were identified that met the selection criteria. The stepwise discriminant procedure resulted in the final selection of 6 optimal regions that most contributed to the discriminatory power of the classification algorithm. Infrared spectra derived from synovial fluid of joints with osteochondrosis were differentiated from the control samples with accuracy of 77% (81% specificity and 73% sensitivity).
Conclusions and Clinical Relevance—The disease-associated characteristics of infrared spectra of synovial fluid from joints with osteochondrosis may be exploited via appropriate feature selection and classification algorithms to differentiate joints with osteochondrosis from those of control joints. Further study with larger sample size including age-, breed-, and sex-matched control horses would further validate the clinical value of infrared spectroscopy for the diagnosis of osteochondrosis in horses.
Objective—To evaluate use of infrared spectroscopy for diagnosis of traumatic arthritis in horses.
Animals—48 horses with traumatic arthritis and 5 clinically and radiographically normal horses.
Procedures—Synovial fluid samples were collected from 77 joints in 48 horses with traumatic arthritis. Paired samples (affected and control joints) from 29 horses and independent samples from an affected (n = 12) or control (7) joint from 19 horses were collected for model calibration. A second set of 20 normal validation samples was collected from 5 clinically and radiographically normal horses. Fourier transform infrared spectra of synovial fluids were acquired and manipulated, and data from affected joints were compared with controls to identify spectroscopic features that differed significantly between groups. A classification model that used linear discriminant analysis was developed. Performance of the model was determined by use of the 2 validation datasets.
Results—A classification model based on 3 infrared regions classified spectra from the calibration dataset with overall accuracy of 97% (sensitivity, 93%; specificity, 100%). The model, with cost-adjusted prior probabilities of 0.60:0.40, yielded overall accuracy of 89% (sensitivity, 83%; specificity, 100%) for the first validation sample dataset and 100% correct classification of the second set of independent normal control joints.
Conclusions and Clinical Relevance—The infrared spectroscopic patterns of fluid from joints with traumatic arthritis differed significantly from the corresponding patterns for controls. These alterations in absorption patterns may be used via an appropriate classification algorithm to differentiate the spectra of affected joints from those of controls.