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PubMedDate not supplied

A prospective randomized trial of thymopentin versus granulocyte--colony stimulating factor with or without thymopentin in the prevention of febrile episodes in cancer patients undergoing highly cytotoxic chemotherapy.

One hundred patients with advanced carcinoma undergoing highly cytotoxic chemotherapy were enrolled in a prospective randomized trial comparing subcutaneous G-CSF, thymopentin, a combination of the two, and placebo as preventive treatment of febrile leukopenia. Data from this study show that G-CSF was very active in reducing the incidence of chemotherapy-related fever and leukopenia as compared to placebo (22% versus 64%). This difference was statistically highly significant (P < 0.001). Thymopentin was associated with a reduction in febrile episodes as compared to placebo (52% versus 64%), but this difference did not reach statistical significance. Moreover, the addition of thymopentin to G-CSF did not result in a statistically significant improvement of results obtained with G-CSF alone. Similar results were achieved for fungal infections. Tolerance to thymopentin was excellent, while less than 9% of patients on G-CSF treatment complained of mild nausea and generalized bone pain.

Adult↗
PubMed1985

In vitro influence of thymopentin on proliferative responses and phytohemagglutinin-induced interleukin 2 production in normal human lymphocyte cultures.

Peripheral human blood lymphocytes from healthy blood donors were investigated in vitro to observe the influence of different doses of thymopentin on nonstimulated proliferation, candidin-stimulated proliferation, and phytohemagglutinin (PHA)-induced interleukin 2 (IL2) production. Concentrations of thymopentin ranging from 0.01 to 10,000 ng/ml were used. The proliferation response in non-stimulated cultures was significantly higher in the presence of 0.01, 1, 10, 1,000, and 10,000 ng/ml of thymopentin. There was no significant increase with 0.1 or 100 ng/ml of thymopentin. Thus, three separate peaks were present in these unstimulated cultures: at a concentration of 0.01 ng/ml; between 1 and 10 ng/ml, and between 1,000 and 10,000 ng/ml. These peaks possibly represent three different subpopulations with different sensitivities to different concentrations of thymopentin. Candidin-induced proliferation was significantly higher only at concentrations of 1 and 10 ng/ml of thymopentin, corresponding to the second peak in the unstimulated culture. No other thymopentin concentrations induced significant increase in the candidin-stimulated cultures. No IL2 production was observed in the unstimulated cultures, even in the presence of thymopentin. On the contrary, preincubation with different concentrations of thymopentin influenced PHA-induced IL2 production. A significant increase in the IL2 level was observed in the supernatant of the cultures if 1,000 ng/ml of thymopentin was used in the preculture period. This concentration corresponds to the third peak in the unstimulated cultures. No significant changes were observed with other concentrations of thymopentin. As the measured value of IL2 is a result of a balance between IL2 production and utilization, the above-mentioned findings need further investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1995

Safety and efficacy of thymopentin in zidovudine (AZT)-treated asymptomatic HIV-infected subjects with 200-500 CD4 cells/mm3: a double-blind placebo-controlled trial.

Thymopentin, 50 mg subcutaneously (s.c.) 3 times per week, was evaluated in a double-blind, randomized, placebo-controlled trial of zidovudine (AZT)-treated asymptomatic human immunodeficiency virus (HIV)-infected subjects with 200-500 CD4 cells/mm3 at entry. The 352 subjects were prestratified by prior AZT use into stratum I (235 subjects, > 6 months AZT at entry) and stratum II (117 subjects, < or = 6 months AZT at entry). Clinical end points, CD4 cell counts, serum p24, serum immune complex dissociated (ICD) p24, and safety variables were evaluated through 48 weeks, using an intent-to-treat analysis. The two strata were analyzed individually because they yielded different clinical outcomes, with a statistically significant treatment-by-stratum interaction. In stratum I (mean, 16 months AZT at entry) two AIDS or death events occurred in thymopentin and 10 in placebo recipients (p = 0.024; relative risk (RR) estimate, 4.9 [95% confidence limit (CI), 1.1 to 22.2]). There were three AIDS-related complex (ARC), AIDS, or death events in thymopentin and 18 in placebo recipients [p = 0.001; RR estimate, 5.9 (95% CI, 1.7 to 20.0)]. In stratum II (mean, 3 months AZT at entry), four AIDS or death events occurred in thymopentin and none in placebo recipients (p = 0.11), and four ARC, AIDS, or death events occurred in thymopentin and two in placebo recipients (p = 0.79). The treatment groups did not differ significantly with respect to changes in CD4 counts or p24 antigen levels or with respect to clinical adverse experiences or laboratory abnormalities. Thus, AZT-experienced placebo-treated subjects had relatively high progression rates to AIDS or death and to ARC, AIDS, or death, and these rates were reduced by thymopentin treatment. In contrast, placebo-treated subjects with little prior AZT experience had low progression rates; these were not significantly changed by thymopentin treatment. There was no increase in the incidence of adverse reactions with thymopentin.

Adult↗
PubMed1994

Impact of thymopentin on the incidence and severity of postoperative infection: a randomized controlled trial.

The effectiveness of perioperative administration of thymopentin in preventing postoperative infection was evaluated in 206 patients with cancer (54 gastric, 152 colorectal) who underwent elective major surgery. Comparable subsets of patients were obtained with respect to age (proportion over 65 years) and nutritional status (patients with serum albumin level less than 30 milligrams or weight loss of 10 per cent or more of usual body-weight were considered to be malnourished). Patients were then randomly assigned to a control group or to a group receiving thymopentin. All patients received perioperative short-term antibiotic prophylaxis and postoperative parenteral nutrition. Levels of CD3-, CD4- and CD8-positive T cell subsets were evaluated before and after surgery in 20 (ten elderly) patients from each group. The severity of postoperative infection was evaluated using a sepsis score. In elderly patients thymopentin prevented the postoperative drop in CD3- and CD4-positive T cell subpopulations that was observed in controls (P < 0.05d). The postoperative infection rate was 17.5 per cent in the group given thymopentin and 24.3 per cent in controls (P not significant). The mean (s.d.) sepsis score was 6.7 (3.1) in the group receiving thymopentin and 9.4 (5.8) in controls (P not significant). Considering only elderly patients, the mean (s.d.) sepsis score was significantly lower in those treated with thymopentin than in control patients (6.9(2.1) versus 11.3(4.7)). In conclusion, administration of thymopentin did not significantly reduce the postoperative infection rate. However, it prevented the drop in number of CD3- and CD4-positive T cells after operation and reduced the severity of postoperative infection in elderly patients.

Adult↗
PubMed1992

Maintenance of CD4+ cells by thymopentin in asymptomatic HIV-infected subjects: results of a double-blind, placebo-controlled study.

OBJECTIVE: To assess the efficacy and safety of thymopentin in HIV-infected patients who had not yet developed AIDS. DESIGN: Patients were stratified into asymptomatic or symptomatic groups and randomized to receive either thymopentin (50 mg) or placebo, subcutaneously, double-blind for 24 or 52 weeks, three times a week. SETTING: Patients were enrolled at three sites (two hospital clinics and one private practice). PATIENTS: Of 91 HIV-seropositive patients (52 asymptomatic and 39 symptomatic) from whom HIV could be isolated from peripheral blood, 45 were enrolled for 24 weeks and 46 for 52 weeks of double-blind evaluation. MAIN OUTCOME MEASURES: Virological, immunological and clinical evaluations were performed before and during treatment. RESULTS: Thymopentin-treated asymptomatic patients had more CD4+ cells, as demonstrated by a greater area under the percentage CD4+ cells curve (P = 0.03) and a shorter median time to a 20% increase in percentage of CD4+ cells (P = 0.04) in the first 24 weeks, with similar trends in the 52-week study. By 24 weeks no asymptomatic thymopentin-treated and two placebo-treated patients (9.1%, Kaplan-Meier estimate) had progressed to constitutional symptoms (P = 0.12; two-tailed Wilcoxon-Gehan test), with only one further progression in a placebo-treated patient in the subset followed for 52 weeks. Symptomatic patients receiving thymopentin or placebo were similar in both CD4+ cell levels and disease progression (two progressions to AIDS in each group). No serious adverse effects attributable to thymopentin were observed. CONCLUSIONS: These results, if confirmed, indicate that thymopentin, by maintaining CD4+ cells, could slow or arrest immune decline and consequent disease progression at the asymptomatic stage of HIV infection.

Amino Acid Sequence↗
PubMed1990

Influence of thymopentin on antibody response, and monocyte and T cell function in hemodialysis patients who fail to respond to hepatitis B vaccination.

We investigated the influence of thymopentin as an adjuvant for hepatitis B vaccination on in vitro monocyte and T cell function and in vivo antibody response in a prospective, placebo-controlled double-blind trial in 20 low- and nonresponders to hepatitis B vaccination on chronic hemodialysis. 50 mg thymopentin was given subcutaneously twice per week for 3 weeks, followed by 1 intramuscular injection of 40 micrograms HB-Vax and 3 subsequent injections of thymopentin. After 1 month, the patients were boostered with 40 micrograms HB-Vax. There was no significant difference in T cell and monocyte function after administration of thymopentin, as determined in vitro. After 3 months, 3 patients in the placebo and 2 patients in the thymopentin group had antibody titers greater than 10 U/l. In both groups only patients with normal or slightly impaired monocyte function responded to vaccination. Thus, we were not able to demonstrate a beneficial effect of thymopentin on hepatitis B vaccination in nonresponders on chronic hemodialysis. Furthermore, functional tests were not able to identify a subpopulation of uremic nonresponders who would benefit from thymopentin.

Adjuvants, Immunologic↗
PubMed1992

Acute beta-interferon or thymopentin administration increases plasma growth hormone and cortisol levels in children.

The interaction between the immune and endocrine systems has recently been investigated. Hodgkin's disease represents a model of immune disturbance frequently associated with endocrine impairment. The present study evaluated the effect of the acute administration of beta-interferon or thymopentin on plasma growth hormone, prolactin and cortisol levels in children with Hodgkin's disease (N = 8) and age- and sex-matched healthy controls (N = 8). beta-interferon (1,000,000 IU), thymopentin (50 mg) or placebo (saline) were injected after two basal blood samples (-15 and 0) and further samples were drawn at 15, 30, 45, 60, 90 and 120 min. Plasma growth hormone, prolactin and cortisol levels were measured by specific RIAs. Plasma prolactin levels did not show significant change following beta-interferon or thymopentin injection in either the controls or the patients. In the patients with Hodgkin's disease, beta-interferon injection induced a significant increase in both plasma growth hormone and cortisol levels, while thymopentin was not effective. In controls both thymopentin and beta-interferon administration increased plasma growth hormone and cortisol levels. These results indicate that beta-interferon and thymopentin are immune substances active on the release of growth hormone and cortisol in healthy children. The lack of effect of thymopentin in children with Hodgkin's disease suggests an impairment of the immune-endocrine interaction in these patients.

Adolescent↗
PubMed1985

Prevention of recurrences in frequently relapsing herpes labialis with thymopentin. A randomized double-blind placebo-controlled multicenter study.

The present randomized, placebo-controlled double-blind multicenter study included a population of 36 subjects with frequent recurrences (at least once a month) of herpes labialis. Most of the patients had failed to respond adequately to previous treatment with other therapeutic tools, including acyclovir. Either 50 mg of thymopentin or of placebo was administered 3 times a week, by the subcutaneous route, for 6 weeks. Subsequently, the patients were observed for nearly 6 months on the average. The results achieved with thymopentin for the individual parameters were significantly superior to those obtained with placebo; thus significant improvement was seen in patients on thymopentin in the duration of the longest symptomfree period (prolonged from 2.1 weeks to 20.9 weeks, p = 0.000), in the number of relapses (reduced from 1.6 to 0.4 episodes/month, p = 0.001), and in the total duration of herpes symptoms per month (shortened from 2.0 to 0.3 weeks, p = 0.000). Placebo treatment also resulted in considerable improvement (p less than 0.05 or 0.01), but was significantly inferior to the improvement obtained with thymopentin. The longest symptomfree period in the placebo group was prolonged from 2.4 to 11.2 weeks. The number of relapses per month was reduced from 1.4 to 0.8, and the total duration of herpes symptoms per month from 2 to 0.9 weeks. The results of intergroup analyses, in which the observed parameters and the improvement achieved in either group were compared, significantly favored thymopentin treatment. The effect of thymopentin was in all but one parameters superior to that of placebo and highly significant (p less than 0.01).

Adjuvants, Immunologic↗
PubMed1990

Thymopentin therapy reduces the clinical severity of atopic dermatitis.

One hundred patients with moderate to severe atopic dermatitis were entered into a two-center, double-blind trial. Patients were randomized to receive either thymopentin (Timunox, n = 48) or placebo (n = 52), administered as daily subcutaneous injections for 6 weeks. Clinical extent of disease and severity parameters were measured at baseline and at regular time intervals during the study. Both the placebo- and thymopentin-treated groups demonstrated a progressive and statistically significant (p less than 0.001) decline in the overall severity of their disease, but reduction in the clinical severity score was higher in the thymopentin-treated group and statistically significant (p = 0.04) in comparison with the placebo-treated group after 6 weeks of treatment. Of the individual symptoms comprising the total severity score, pruritus (p = 0.02) and erythema (p = 0.04) were reduced significantly when thymopentin therapy was compared to placebo therapy. In addition, both the extent of body involvement and severity index (a combined severity/extent index) were significantly reduced after 6 weeks in the thymopentin-treated group in comparison to the placebo-treated group (p = 0.04). There were no serious adverse experiences in either treatment group. We conclude that treatment with thymopentin is safe and offers significant therapeutic promise for atopic dermatitis.

Adolescent↗
PubMed1990

Thymopentin antagonizes stress-induced changes of GABA/benzodiazepine receptor complex.

Intraperitoneal administration of thymopentin, a thymopentin II-derived pentapeptide, had no stable and evident effect in the two anxiety models (elevated plus-maze and licking-conflict test) studied. However, in the elevated plus-maze test thymopentin antagonized the behavioral effects of DMCM, a beta-carboline derivative with anxiogenic properties. Further, it was demonstrated that the licking-conflict test procedure itself produced a significant elevation of plasma corticosterone levels, increased the number of [3H]flunitrazepam and decreased the number of [3H]muscimol binding sites in rat hippocampus. The forced-swimming stress similarly to the licking-conflict test also caused an increase in hippocampal [3H]flunitrazepam binding sites. Although ineffective behaviorally in the tests for anxiety, thymopentin pretreatment effectively reversed the changes in corticosterone levels caused by the licking-conflict test. Moreover, it normalized the changed number of benzodiazepine and GABA receptors after stressful stimuli. It is well known that not all anxiolytic drugs (i.e. buspirone) are equally active in behavioral tests for anxiety. According to our data we propose that thymopentin has stress-protective activity. As in vivo and in vitro thymopentin did not change [3H]-flunitrazepam and [3H]muscimol binding, the direct effect of this peptide on the GABA-benzodiazepine-Cl- ionophore receptor complex is unlikely. The action of this peptide on GABA release and/or metabolism can be suggested.

Animals↗
PubMedDate not supplied

Radioprotective effects of the association thymopentin-interleukin-1 alpha in the C57BL/6 mouse.

We investigated whether thymopentin, a synthetic pentapeptide derivative of thymopoietin, could enhance the protective effect of interleukin-1 alpha when both administered prior to sublethal irradiation in the C57BL/6 mouse. Thymopentin (10 mg/kg/day/7 days) was injected intraperitoneally in groups of C57BL/6 mice. Then, interleukin-1 alpha was administered on day 7. Twenty hr later, all groups were given whole body sublethal irradiation of 750 rad by 60Co elements. In some groups of mice, treatment with thymopentin was continued for 1 week after irradiation. Efficacy of the combination treatment was assessed by evaluation of mortality, as well as by histologic examination of the brain, testis, bone marrow, heart and spleen. The combination of relatively low doses of interleukin-1 alpha (700 U) with thymopentin yielded a survival which was nearly that observed with interleukin-1 alpha (1000 U) given alone (about 100%). The optimal effect was observed in animals treated for 15 days with thymopentin, either in combination or alone. In addition, incidence and severity of histological lesions were also lower in animals with the some treatment schedule. Our results suggest that the combined treatment thymopentin-interleukin-1 alpha prevents radiation damage in the mouse.

Animals↗
PubMed1992

Thymopentin treatment in severe atopic dermatitis--clinical and immunological evaluations.

An open clinical trial of thymopentin was conducted on 16 children with severe atopic dermatitis. The patients were treated with injections three times a week of 50 mg thymopentin for six weeks. They were then divided randomly into two groups: group A continued thymopentin for an additional six weeks, and group B were treated with normal saline. Clinical parameters and immunological function were evaluated serially. The total severity score started to decline from baseline significantly three weeks after treatment, and continued throughout the study period in group A but began to flare up in group B two weeks after stopping thymopentin. All the eight patients in group A completed the trial but three out of eight in group B dropped out because of flaring up of skin lesion. In vitro production of interleukin-4 tended to decrease and that of interferon gamma tended to increase, but total serum IgE, in vitro IgE synthesis, and abnormally low CD8+ CD11b+ suppressor T cells remained unchanged. Histamine releasing factor (HRF), plasma histamine, and respiratory burst activities of polymorphonuclear leucocytes were appreciably decreased after thymopentin treatment. It is concluded that the clinical efficacy of short term thymopentin treatment very possibly results from the decreased production of HRF and decreased release of polymorphonuclear leucocyte derived inflammatory mediators and may have no relation with antigen-IgE immune reaction.

Adolescent↗
PubMedDate not supplied

Thymopentin increases the survival of mice after allogeneic blood transfusion, bacterial gavage, and burn injury.

OBJECTIVE: To investigate the effect of blood transfusion on mortality and the incidence of bacterial translocation in mice subjected to thermal burn or bacterial gavage, or both, and to assess the influence of thymopentin on mortality. DESIGN: Randomly controlled experiments. SETTING: University departments of surgery, immunology and nuclear medicine. MATERIAL: 235 Balb/c (H-2d) and C3H/HeJ (H-2k) mice. INTERVENTIONS: 8 groups of 20 mice each received: saline infusion (controls), blood transfusion (BT) alone, 20% burn alone, gavage with 1 x 10(10) Escherichia coli alone, BT and gavage, BT and burn, burn and gavage, or BT, burn, and gavage. A further 3 groups of 10 mice were all gavaged with 111In-biotin labelled E coli and randomised to additional BT and burn, BT alone, or burn alone. 98 mice that had had BT, burn, and gavage, were then randomised to receive thymopentin 0, 0.1, 1, or 5 mg/kg/day for 15 days. The impact of the pretreatment with thymopentin on PGE2 concentration was also evaluated in a separate group of 45 mice that received BT, burn, and gavage; or burn and gavage. MAIN OUTCOME MEASURES: Survival, degree of translocation. RESULTS: The highest mortality (75%) was in the BT, burn, and gavage group. BT alone significantly reduced survival in burned mice, whereas BT alone or associated with gavage had no effect. Thermal injury had the most influence on bacterial translocation, whereas BT did not increase it. Thymopentin significantly improved survival, particularly in the higher doses. The pretreatment with thymopentin significantly reduced PGE2 concentration after BT, burn and gavage. CONCLUSION: Burn injury significantly increased mortality in the presence of immune deficiency caused by BT. Thymopentin reduced mortality, possibly by immunomodulation.

Animals↗
PubMed1985

Effect of thymopentin on the mortality and immune response after an experimental herpes simplex infection in mice.

The effect of thymopentin on the mortality rate of mice treated with lethal doses (LD90) of herpes virus 2 and on the cytotoxic T cell activity after sublethal doses (LD10) of herpes virus was investigated in two series of experiments. Doses of 1, 0.1 or 0.01 ng of thymopentin per g/mouse were administered i.p. in each experiment, either 3 days before, 3 days (66 h) after, or 3 and 6 days after the herpes virus infection. The cumulative mortality rate was evaluated 10 days after the infection. Cytotoxic T cell activity was measured 3, 7 and 14 days after the infection. The 0.1-ng dose of thymopentin reduced the mortality rate to less than 50% (p = 0.0000) if it was administered 3 days before the infection. A single injection of any dose after infection did not reduce the mortality at all, while two injections of 0.1 ng reduced it by about 25% (p = 0.0038). A 1-ng dose showed a mild but significant reduction (p = 0.0313) if it was applied 3 days before the infection. The cytotoxic T cell activity was either not influenced or significantly modified (p less than 0.05), i.e. increased or decreased as compared to the control, depending on the dose and timing of thymopentin. A correlation between increased cytotoxic T cell activity and protection against mortality can be demonstrated, while no protection was observed in dose regimens where the cytotoxic T cell activity became reduced. The results are discussed in connection with earlier clinical studies in which the beneficial effect of thymopentin has been demonstrated in frequently relapsing herpes labialis and herpes genitalis patients.

Adjuvants, Immunologic↗
PubMed1985

Thymopentin treatment in AIDS and pre-AIDS patients.

Three pilot studies testing thymopentin in AIDS patients are presented. One study included 5 patients with the full-blown syndrome, all treated with 50 mg thymopentin 3 times a week by intravenous slow infusion; no immunologically nor clinically positive results were observed, indicating that the T cell pool in such patients is severely depleted. Six other patients with the prodromal stage of AIDS were treated 1 month with 50 mg thymopentin administered as an intravenous bolus injection 3 times weekly and thereafter for another month with same dose regimen as intravenous slow infusions. The patients on infusion therapy experienced statistically significant immunological improvements; these positive findings were paralleled with an improvement of the patients' clinical condition. These positive responses persisted for an average of 8 months. In another group of 5 pre-AIDS patients thymopentin was administered via the subcutaneous route using 15 mg 3 times weekly; only 1 patient revealed immunological and clinical improvement. In summary, only patients with the pre-AIDS syndrome are likely to benefit from immunomodulation therapy with thymopentin, and the mode of administration seems to be crucial.

Acquired Immunodeficiency Syndrome↗
PubMed1990

An aminoboronic acid derivative inhibits thymopentin metabolism by mucosal membrane aminopeptidases.

Thymopentin is a pentapeptide with immunomodulatory activity. Transmucosal delivery may offer advantages over other routes, but published data have shown relatively poor efficacy when dosed nasally. Metabolism of thymopentin by the rat nasal mucosa and the effects of an aminoboronic acid aminopeptidase inhibitor, boroleucine, were evaluated. Thymopentin concentrations in a solution perfused through the isolated nasal cavity decayed with a first-order half-life of 12 minutes. Thymopentin was metabolized primarily by aminopeptidases, based on the amount of tetrapeptide metabolite formed. In the presence of boroleucine, at an inhibitor/substrate molar concentration ratio of 0.015/1, the degradation half-life was prolonged to 37 minutes. Appearance of the tetrapeptide metabolite of aminopeptidases was delayed. Boroleucine and other aminoboronic acid peptidase inhibitors may be useful for improving thymopentin delivery.

Amino Acid Sequence↗
PubMed1994

A double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of thymopentin as an adjunctive treatment in atopic dermatitis.

BACKGROUND: Multiple immunologic abnormalities such as impaired T-cell function, elevated serum IgE level, and increased interleukin 4 production have been demonstrated in patients with atopic dermatitis. OBJECTIVE: As part of a 12-week, multicenter, double-blind, placebo-controlled clinical trial, we evaluated the safety and efficacy of thymopentin (Timunox) as an adjunctive treatment in patients with severe atopic dermatitis. METHODS: Thirty-nine patients at least 2 years old with severe atopic dermatitis on a minimum of 20% of their cutaneous surface area were randomly selected to receive either thrice-weekly subcutaneous injections of thymopentin, 50 mg, or placebo. Use of triamcinolone 0.1% or hydrocortisone 1.0% cream and oral antihistamines were permitted during this trial. RESULTS: After 12 weeks, thymopentin-treated patients had significantly greater improvement than those receiving placebo. No thymopentin-related adverse events occurred. CONCLUSION: Thymopentin may be a safe effective adjunct to therapy in patients with severe atopic dermatitis.

Adolescent↗
PubMed1998

Isothermal and nonisothermal decomposition of thymopentin and its analogs in aqueous solution.

PURPOSE: The degradation kinetics of thymopentin (RKDVY) and its analogs (RKDVW and RPDVY) in aqueous solution was studied by isothermal and nonisothermal methods. METHODS: The isothermal decomposition of thymopentin and its analogs was investigated as a function of pH (2-10), temperature (37, 57, and 80 degrees C) and ionic strength (micro = 0.02 to 1). Nonisothermal decomposition studies were performed using a linear temperature programmer. The temperature increasing rate was set to 0.25 degrees C per hour and the temperature interval varied from 40 to 88 degrees C. RESULTS: The decomposition of thymopentin and its analogs followed first order kinetics. The dependence of the rate constant on temperature followed a linear Arrhenius plot. This indicated that the degradation mechanism of thymopentin and its analogs might be the same within the temperature range studied. The energies of activation were found to be in close agreement for the isothermal and nonisothermal studies, suggesting that the nonisothermal studies may save considerable amount of time in the early stages of drug development. The logK-pH profile of thymopentin suggests that maximum stability is achieved in the pH range of 6-8. CONCLUSIONS: These results indicate that the nonisothermal methodology provides an attractive alternative to isothermal methods, as it requires a much lower amount of both material and time, to determine the peptide stability and to estimate the shelf-life for peptide pharmaceutical preparations.

Drug Stability↗