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Biomedical subjects

P Periti

Publications and source records attributed to P Periti.

At least 91 records · Page 5Linked to original sources
PubMed1989

Clinical pharmacokinetics and tissue penetration of teicoplanin.

The pharmacokinetic properties were investigated of teicoplanin, including its penetration into suction blister fluid (SBF), after a single intravenous bolus administration of 600 mg in seven pneumological patients with normal renal and hepatic function. Blood and SBF samples were collected during the 60-hour period drug administration. Teicoplanin was assayed microbiologically and the mean serum concentration at the end of the i.v. injection was 98.7 +/- 16 mg/l falling to 2.3 +/- 0.4 mg/l at 60 h. The antibiotic was rapidly distributed into a fast equilibrating peripheral compartment and, at a lower rate, into a slowly equilibrating peripheral compartment, while the mean elimination half-life (t1/2 beta) was 34.1 +/- 6.8 h. Penetration into the SBF, though slow, was good, reaching a mean peak level of 8.7 +/- 1.7 mg/l at a mean time of 2.1 h, with a penetration index (obtained by percentage ratio of the area under curve in the SBF to that of serum) of 42.9%.

Adult↗
PubMed1989

Pharmacokinetics of teicoplanin during cardiopulmonary bypass surgery.

Teicoplanin is a recently introduced long-acting glycopeptide antibiotic effective against Gram-positive aerobic and anaerobic bacteria. The effects of hypothermic extracorporeal circulation on teicoplanin serum pharmacokinetics have been studied in 18 patients undergoing open-heart surgery for coronary artery bypass graft or prosthetic cardiac valve insertion. The patients received a single 600 mg dose of teicoplanin by intravenous (i.v.) bolus (five cases) or by i.v. infusion over 20 min (13 cases) approximately 1 h before the anticipated skin incision and 2 h before the anticipated extracorporeal circulation. Serum drug concentrations were measured by a microbiological method using Bacillus subtilis ATCC 6633 as the test organism. Following i.v. bolus injection and i.v. infusion, teicoplanin levels in serum (mean +/- s.d.) were respectively 13.9 +/- 6.8 and 11.4 +/- 2.4 mg/l at the beginning of extracorporeal circulation, 8.8 +/- 3.5 and 10.2 +/- 2.3 mg/l at the end of this procedure and 2.8 +/- 0.6 and 2.9 +/- 1.0 mg/l at 24 h after surgery. Mean AUCs were 378.1 +/- 52.5 and 328.9 +/- 88.0/l.h and mean elimination half-life values were 27.9 +/- 12.7 and 30.3 +/- 11.0 h, respectively under the same conditions. These differences in plasma pharmacokinetic parameters were not significant. Teicoplanin pharmacokinetics in patients undergoing cardiopulmonary bypass surgery were similar to those observed in non-surgical patients with normal renal and hepatic function, confirming experimental evidence for lack of effects of extracorporeal circulation.

Bacterial Infections↗
PubMed1988

Impaired polyglutamylation of methotrexate as a cause of resistance in CCRF-CEM cells after short-term, high-dose treatment with this drug.

Two methotrexate-resistant sublines, CCRF-CEM R3/7 and CCRF-CEM R30/6, were selected from the human leukemia T-lymphoblast cell line, CCRF-CEM, after repeated exposures (7 and 6 times, respectively) for 24 h to constant concentrations (3 and 30 microM) of the drug. Analysis of the mechanism of resistance revealed no differences in levels of dihydrofolate reductase activity, its binding affinity for methotrexate, or in methotrexate transport between the CCRF-CEM parent and methotrexate-resistant cell lines. The development of resistance to methotrexate was associated with a marked decrease in the intracellular level of methotrexate polyglutamates. Although the resistant sublines were able to form substantial amounts of folate polyglutamates when measured with [3H]folic acid, the level of polyglutamates formed was decreased to about 50% of that formed by the parent cell line. No qualitative differences in folate polyglutamates formed were noted between the parental and resistant sublines. This is the first example of a cell line which displays resistance which is solely attributable to defective methotrexate polyglutamate synthesis.

Drug Resistance↗
PubMed1988

Comparison of the antimicrobial prophylactic efficacy of cefotaxime and cephazolin in obstetric and gynaecological surgery. A randomised multicentre study.

A prospective randomised multicentre study was designed to assess the efficacy of 2 different cephalosporins as short term prophylactic treatment in obstetric and gynaecological surgery. A single dose of cefotaxime (2g IV before surgery) was compared with 2 doses of cephazolin (2g IV before surgery and after 8 hours). Patients exposed to antibacterial drugs within 7 days, who had preoperative infections, or with known beta-lactam hypersensitivity were excluded. 612 patients entered the study, of whom 552 were evaluable. 276 were given cephazolin (group A) and 276 cefotaxime (group B). Groups A and B were similar for mean age, obesity, diabetes, types of diseases and obstetric history. No significant differences were observed in type of surgery (vaginal hysterectomy, abdominal hysterectomy, myomectomy and caesarean section) between 2 groups. The mean duration of surgery was 89 and 85 minutes in group A and B, respectively. 25 patients (9.1%) in group A and 20 (7.2%) in group B developed wound infections (not statistically significantly different). The percentages of patients with infections other than surgical infections were similar (i.e. 13.0 and 11.2 for the cefotaxime and the cephazolin groups, respectively). These preliminary data show that a single 2g IV dose of cefotaxime and two 2g IV doses of cephazolin have equal antimicrobial prophylactic activity in obstetric and gynaecological surgery.

Adult↗
PubMed1988

Prophylaxis in gynaecological and obstetric surgery: a comparative randomised multicentre study of single-dose cefotetan versus two doses of cefazolin.

Antimicrobial prophylaxis is recommended in all clean-contaminated surgery where the critical threshold of number and virulence of the contaminating organisms with respect to host resistance is reached. Obstetric and gynaecological surgery is clean-contaminated and risk of infection due to aerobic and anaerobic bacteria without prophylaxis can be quantified at 30-40% for vaginal hysterectomy, 10-35% for abdominal hysterectomy and 10-34% for caesarean section. To assess the role of two different cephalosporins as short term prophylaxis, we carried out a multicentre randomised study involving a single 2 g i.v. dose of cefotetan in comparison with two doses of cefazolin (2 g i.v. before surgery and after 8 hours). Criteria for exclusion were: exposure to antibiotics within 7 days, preoperative infection, hypersensitivity to beta-lactams. Four hundred and sixty patients entered the study, of which 229 received cefotetan and 231 cefazolin. No significant differences in mean age, obesity, preoperative weight loss, diabetes, type of disease, type of surgery (vaginal or abdominal hysterectomies and caesarean sections) and number of pregnancies and abortions existed between the two groups of patients. The total rate of infected patients undergoing hysterectomy was 8.6% (13/151) in the cefotetan group and 17.4% (29/167) in the cefazolin group (p less than 0.05). This difference was due to cases of symptomatic bacteriuria and antibiotic retreatment, while wound infections were not significantly different (2.6% and 1.8% respectively). Among patients undergoing caesarean section, 9 of 78 (11.5%) and 7 of 64 (10.9%) were infected following cefotetan and cefazolin, respectively (not significant). Cefotetan mean tissue concentrations in gynaecological organs were higher than those of cefazolin (25.5-44.8 vs. 7.4-9.5 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Ceftizoxime concentrations in human aqueous humor following intravenous administration.

The aqueous humor penetration of the third-generation cephalosporin, ceftizoxime, was determined in 21 patients awaiting cataract extraction, after an intravenous bolus injection of 2 g. The beta-lactam compound achieved a mean peak aqueous humor concentration of 7.8 mg/l two hours after administration with a serum/humor percent ratio ranging between 7 and 16% during the four-hour sampling interval. Therefore, ceftizoxime levels in this extravascular fluid were above the minimum inhibitory concentrations for the majority of sensitive organisms.

Adult↗
PubMed1987

Effects of 5-methyltetrahydrofolate on the activity of fluoropyrimidines against human leukemia (CCRF-CEM) cells.

The growth inhibitory effects of 5-fluorouracil (FUra) or 5-fluoro-2'-deoxyuridine (FdUrd) combined with 5-methyltetrahydrofolate (5-CH3-H4PteGlu) were determined, as a function of time, dose, and sequence of exposure, on human T-lymphoblast leukemia cells, CCRF-CEM. Synergistic inhibitory effects on cell growth were obtained when exponentially growing CCRF-CEM cells were exposed to 5-CH3-H4PteGlu (1-100 microM) for 4 hr and to FUra (250 microM) or FdUrd (0.5 microM) during the last 2 hr. Synergism was dependent on 5-CH3-H4PteGlu dose (100 greater than 10 greater than 1 microM) and did not occur at 0.1 microM. No clear dependence of synergism on sequence was observed with FUra and 5-CH3-H4PteGlu combinations (5-CH3-H4PteGlu----FUra,5-CH3-H4PteGlu + FUra, or FUra----5-CH3-H4PteGlu). With 5-CH3-H4PteGlu and FdUrd combinations, synergism was dependent on sequence of exposure (5-CH3-H4PteGlu + FdUrd, 5-CH3-H4PteGlu----FdUrd were synergistic, but FdUrd----5-CH3-H4PteGlu was not). Thymidine (0.1 microM), added after drug treatment, substantially rescued CCRF-CEM cells from 5-CH3-H4PteGlu----FUra cytotoxicity. L-methionine (1500 mg/l) completely protected CCRF-CEM cells from enhanced cytotoxicity of the combination, 5-CH3-H4PteGlu-FdUrd. The results are consistent with the hypothesis that the mechanism by which 5-CH3-H4PteGlu potentiates fluoropyrimidine cytotoxicity is the enhancement of complex formation between thymidylate synthase and 5-fluorodeoxyuridylate, as a consequence of an increase of intracellular levels of 5,10-methylenetetrahydrofolate generated from 5-CH3-H4PteGlu. Also, enhanced stability of the complex in the presence of high levels of this folate coenzyme may contribute to the synergism observed. These data provide a rationale basis for further trials of folate coenzymes and fluoropyrimidine combinations in the clinic.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Pharmacokinetics of roxithromycin in renal and hepatic failure and drug interactions.

In patients with renal insufficiency roxithromycin pharmacokinetic parameters are significantly altered. In particular, the Cmax, the AUC and the T1/2 are increased and the Clr is reduced. In alcoholic cirrhotic patients the blood half-life is dosage higher than in normals. In spite of this, in these types of patients the usual roxithromycin dosage should not be modified. Potential pharmacokinetic drug interactions that involve roxithromycin are very few and concern only disopyramide and theophylline. Theophylline concentrations should be monitored if the pretreatment blood level is greater than 15 mg/l.

Aged↗
PubMed1987

Prophylactic chemotherapy with fosfomycin trometamol salt during transurethral prostatic surgery: a controlled multicenter clinical trial.

A prospective, randomized controlled study was carried out in 24 Italian urology wards in 675 patients undergoing transurethral prostatic resection, utilizing three different chemoprophylactic treatments with either amoxycillin (AMX), co-trimoxazole (CTX) or fosfomycin trometamol salt (FT) in order to prevent postoperative urinary tract infections. FT significantly lowered the incidence of both postoperative bacteriuria and symptomatic infections in comparison to AMX and CTX. Transient side effects, mild or moderate, were observed in 6.6% of cases. Similar safety and protective results were obtained in 233 patients undergoing different transurethral instrumentations who were chemoprophylactically treated with FT.

Aminoglycosides↗
PubMed1987

Principles of antimicrobial chemoprophylaxis in surgery.

In the last fifteen years great efforts have been made to establish the appropriate use of antimicrobial agents in surgery. The most common error in the use of prophylactic antibiotics is to continue the drugs beyond the time necessary for maximal benefit: the smallest dose of the drug should be given over the shortest period of time which results in a low rate of postoperative septic complications. In the selection of appropriate antimicrobial drugs for prevention or therapy of surgical infections the most important pharmacological and clinical factors affecting the choice are considered.

Anti-Bacterial Agents↗
PubMed1987

Immunomodulation by cancer chemotherapeutic agents.

Cytotoxic agents may specifically interfere with the different components of cellular and humoral immunity, and consequently modulate the responses in opposite directions, by not only inducing impairment but also augmenting some immune functions. They may also modulate tumor antigenic expression, leading to increased immunogenicity. Glucocorticoids at sufficiently high concentrations can inhibit virtually any function of lymphocytes, NK cells, monocytes and macrophages. Azathioprine and other antimetabolites, such as 6-mercaptopurine, methotrexate and cytarabine, have a similar generalized immunosuppressive activity and may be used therapeutically for this purpose in the clinic. Cyclophosphamide exerts an immunosuppressive or an immunostimulating effect when given at high or low doses, respectively. The marked Cy-induced inhibition of T suppressor lymphocytes, the predominant immune cell population in cancer patients favoring tumor growth, may have important therapeutic significance. DX enhances proliferation of lymphocytes in the presence of mitogens, but may inhibit antibody production; it also increases the tumoricidal activity of monocytes and macrophages and does not alter substantially NK cytolytic activity. A detailed study of drug effects on the tumor and host immune system may contribute to their more rational use in cancer chemotherapy with regard to toxicity and efficacy.

Adjuvants, Immunologic↗
PubMed1987

Comparative in vitro activity of ciprofloxacin, ofloxacin and pefloxacin against resistant clinical isolates.

The in-vitro antimicrobial activity of three new quinolones, ciprofloxacin, ofloxacin and pefloxacin, was compared against 194 recent clinical isolates, 50 S. aureus, 50 E. coli, 45 E. cloacae and 49 P. aeruginosa. About half of the strains were resistant to a standard reference antibiotic like oxacillin (S. aureus), ampicillin (E. coli), gentamicin (E. cloacae) and amikacin (P. aeruginosa). The resistant selected strains were less susceptible to the three fluoroquinolones tested than the parent isolates, but, except for pefloxacin against E. cloacae and P. aeruginosa, the decrease in susceptibility was relatively low and MICs remained below the resistance break-point.

Anti-Bacterial Agents↗
PubMed1987

Ciprofloxacin inhibition of cefoxitin betalactamase induction in an Enterobacter cloacae strain.

The betalactamase activity of an Enterobacter cloacae strain was measured using subinhibitory concentrations of cefoxitin and ciprofloxacin respectively as enzyme inducer and induction inhibitor. Cultures of this strain were also exposed to different ceftriaxone concentrations either alone or in the presence of cefoxitin and/or ciprofloxacin. Ciprofloxacin at subinhibitory concentrations does not interfere with ceftriaxone's activity and is capable of neutralizing the antagonistic effect of cefoxitin on ceftriaxone. The enzyme assay and MS-2 System demonstrate ciprofloxacin's partial suppression of cefoxitin betalactamase induction in the E. cloacae strain tested.

Cefoxitin↗
PubMed1987

Microbiological and pharmacokinetic evaluation of cefonicid, a long-acting cephalosporin.

The in vitro antimicrobial activity of cefonicid has been tested against 27 recent clinical isolates of 7 different species (S. aureus, E. coli, K. pneumoniae, P. mirabilis, S. marcescens, E. cloacae and P. aeruginosa) using the MS-2 Research System, contrast phase microscopy and the colony forming unit assay. With the exception of P. aeruginosa, S. marcescens and E. cloacae, cefonicid showed excellent activity against the different bacterial species tested (i.e. S. aureus, E. coli, K. pneumoniae and P. mirabilis). Tissue penetration of cefonicid after a single i.m. or i.v. dose (1 or 2 g, respectively) was also studied using the suction blister method. In 14 adult subjects with normal renal and liver functions, cefonicid plasma half-life was 5.1 and 5.4 h following i.v. and i.m. administration. Drug concentrations achieved at peak in plasma and suction blister fluid were higher than the minimum inhibitory concentrations for most sensitive pathogens and remained above these values for 24 h. These data support the use of a single daily dose regimen of cefonicid, both i.v. and i.m., for the treatment of most common infections caused by sensitive pathogens in blood and tissues.

Bacteria↗