Biomedical subjects

P Garzone

Publications and source records attributed to P Garzone.

6 recordsLinked to original sources

PubMed1998

Preclinical studies of recombinant factor IX.

Recombinant factor IX (rFIX) has been extensively evaluated in preclinical studies. Dog model study of hemophilia B indicated that rFIX was as effective as a highly purified plasma-derived replacement factor in normalizing indices of hemostasis. Pharmacokinetic studies indicated a dose-proportional profile for rFIX. Pharmacokinetic/pharmacodynamic analysis showed that increases in the plasma concentration of rFIX following administration were closely correlated with measured factor IX activity in the plasma. Appropriate in vitro and in vivo toxicology studies have been performed to support the clinical use of rFIX for the treatment of hemophilia B. Finally, experiments in a model of thrombogenicity indicated that in animals rFIX has a low thrombogenic potential. The preclinical results provided a basis for proceeding with human clinical trials.

Animals↗

PubMed1998

Clinical evaluation of recombinant factor IX.

The pharmacokinetics, safety, and efficacy of recombinant factor IX (rFIX) have been evaluated in previously treated and untreated patients with hemophilia B. In a study of 56 previously treated patients, there was a total of 1,070 hemorrhages, which required 1,514 infusions of rFIX. Of the 1,070 episodes, 80% resolved after a single rFIX infusion. The majority of the remaining episodes requiring more than 1 infusion were either major or complicated hemorrhages. Eighty-seven percent of the 1,514 infusions were rated by the physicians or patients as providing an excellent or good response. These results are consistent with the efficacy data from other hemophilia product clinical trials. rFIX has also been administered as bolus doses or by continuous infusion in conjunction with 13 surgical procedures. Estimated blood loss during and after surgery was as expected when compared with blood loss for similar procedures in patients without hemophilia, and 97% of the clinical responses during and after surgery were rated by physicians or patients as excellent or good. Pharmacokinetic comparison of rFIX with one plasma-derived product showed a statistically significant lower recovery (28% less) of rFIX. The half-lives between the two products were comparable. Common adverse events associated with rFIX treatment have been comparable to other factor IX products. As expected, there has been no evidence of viral transmission by rFIX.

Drug Evaluation↗

PubMed1987

Pressure ulcers.

Pressure sores occur when prolonged pressure or shear is applied to the skin of predisposed patients. Prevention requires identification of patients at risk and institution of thorough surveillance and nursing care. Once pressure ulcers occur, treatment decisions are based on the depth of the ulceration. Management consists of motivating the staff, relieving the pressure, debriding the wound, lowering wound bacterial counts and treating complications.

Anti-Infective Agents, Local↗

PubMed1983

Third-generation and investigational cephalosporins: II. Microbiologic review and clinical summaries.

In vitro susceptibility of Streptococcus pyogenes, Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Serratia marcescens, Hemophilus influenzae, Bacteroides fragilis, and Neisseria gonorrhea to three new second-generation and eight third-generation cephalosporins is tabulated. In general, the newer cephalosporins have an extended spectrum of activity against gram-negative bacteria, including Serratia marcescens, Pseudomonas aeruginosa, and Neisseria gonorrhea. They also tend to be active against anaerobes, including Bacteroides fragilis. However, they generally have less activity against gram-positive bacteria when compared with the first- and second-generation cephalosporins. Clinical summaries are given for each of the cephalosporins, with emphasis on the results of comparative clinical trials. These cephalosporins may prove especially useful in nosocomial infections with resistant organisms, intraabdominal infections, febrile episodes in the granulocytopenic patient, and meningitis.

Bacteria↗

PubMed1981

Steady-state moxalactam kinetics: comparisons with other cephalosporins.

Moxalactam is a new beta-lactam antimicrobial with an extended spectrum. Serum concentrations were determined in 14 patients at steady state using bioassay and high-pressure liquid chromatography methods. Mean peak and trough serum concentrations were 195 and 29.5 micrograms/ml for the 20-gm dose and 214 and 28.8 micrograms/ml for the 3-gm dose. Peak and trough levels exceeded the minimum inhibitory concentration of the infecting bacteria in 100% and 67% of the patients. The 3-gm dose is recommended for infections caused by Pseudomonas aeruginosa and other organisms with higher minimum inhibitory concentrations. Half-lifes ranged from 1.7 to 5.7 hr and reflected the varying renal functions of the patients. A relationship (r = 0.878, p less than 0.001) between creatinine clearance and elimination rate constant was established by bivariant linear regression analysis.

Adult↗

PubMedDate not supplied

Third-generation and investigational cephalosporins: I. Structure-activity relationships and pharmacokinetic review.

The structure-relationships and pharmacokinetic properties of the new second- and third-generation cephalosporins are reviewed. The new second-generation cephalosporins include ceforanide, cefotiam, and cefuroxime. The third-generation cephalosporins include cefmenoxime, cefoperazone, cefotaxime, cefsulodin, ceftazidime, ceftizoxime, ceftriaxone, and moxalactam. These new cephalosporins are semisynthetic analogs with different chemical substitutions on a 7-aminocephalosporanic nucleus. As a result of these chemical modifications, improvements in the antibacterial spectrum as well as pharmacokinetic properties have occurred. In general, the new cephalosporins have longer half-lives, higher and prolonged serum concentrations, and increased cerebrospinal fluid penetration. Selected cephalosporins also have increased biliary tract concentrations. A classification scheme for these new agents, based on generation and susceptibility to Pseudomonas aeruginosa, is presented.

Bacteria↗