Phase 1 study of the iodine absorption, safety, and tolerability of a 0.5% povidone-iodine nasal spray (Nasodine).

KEY POINTS: PVP-I is a widely used antiseptic but only recently proposed for intranasal use. The extent of iodine absorption from available PVP-I nasal products is unknown. Iodine absorption from use of Nasodine (0.5% PVP-I nasal spray) is not clinically significant.

Povidone-iodine pharmacokinetics and study design.

Dr. Gnanasekaran et al. reported the bactericidal activity of various concentrations of povidone iodine (PI) solution in an agar plate experiment of respiratory flora. The study design and the pharmacokinetic properties of PI solution ensured that dilute PI would not be effective in this study. These results may not replicate the typical clinical situation and are significantly different than a previously reported agar plate experiment, again owing to subtle but very significant differences in methodology.

Peritoneal lavage with povidone-iodine solution in colorectal cancer-induced rats.

BACKGROUND: Although peritoneal lavage with povidone-iodine (PVPI) is frequently performed after surgery on the gastrointestinal tract, the effects of PVPI on the intestinal epithelial barrier are unknown. The purpose of this study was to investigate the effects of abdominal irrigation with PVPI on the intestinal epithelial barrier in a colorectal cancer (CRC)-induced rat model. MATERIALS AND METHODS: The CRC model was induced in rats with azoxymethane and dextran sodium sulfate. Next, a total of 24 male CRC-induced rats were randomly divided into three groups (n = 8): (1) a sham-operated group, (2) an NS group (peritoneal lavage 0.9% NaCl), and (3) a PVPI group (peritoneal lavage with 0.45%-0.55% PVPI). The mean arterial pressure was continuously monitored throughout the experiment. The levels of plasma endotoxin and D-lactate, blood gases, and protein concentration were measured. The ultrastructural changes of the epithelial tight junctions were observed by transmission electron microscopy. RESULTS: The mean arterial pressure after peritoneal lavage was lower in the PVPI group than that in the NS group. The protein concentration and levels of endotoxin and D-lactate were higher in the PVPI group than they were in the PVPI group. In addition, PVPI treatment resulted in a markedly severe metabolic acidosis and intestinal mucosal injury compared with NS rats. CONCLUSIONS: Peritoneal lavage with PVPI dramatically compromises the integrity of the intestinal mucosa barrier and causes endotoxin shock in CRC rats. It is unsafe for clinical applications to include peritoneal lavage with PVPI in colorectal operations.

Minimal effective dose of povidone-iodine in abdominal surgery Our clinical experience.

UNLABELLED: The aim of this study is to evaluate the thyroid function tests in order to examine whether 10 % of Povidone-Iodine(PI), the medication we applied in 1/5 ratio diluted with 0.9 %NaCl, joins the systemic circulation during clean contaminated, contaminated and dirty operations for solid organ hydatid cysts in abdominal area to avoid abscess formation and spreading. 7 men and 6 women were included to the present study, prospectively. The mean age was 33.69(± 13.49). TSH, free T3 (fT3) and free T4 (fT4) hormone levels were measured before the operation and at the third day of postoperative period. Amount of used povidone-iodine for patients was recorded. As a result of statistical analysis applied, the preoperative and post operative values were not significantly different regarding with the measured hormone levels (preTSH vs postTSH: p= 0.984; prefT3 vs postfT3: p= 0.101; prefT4 vs postfT4: p=0.146). Thus, it has been shown that the dose we used is effective, and it does not enters at all or at quite low levels into the systemic circulation. Patients whom this application performed, abscess and intestinal adhesions have not been observed in our clinical experience. We recommend the use of suggested doses of Povidone-Iodine in the presence of intraabdominal perforation and abscess or in cases such as carrying a risk of cyst spreading to intraabdominal area in hydatid cysts. KEY WORDS: Povidone-iodine, Surgical adhesions, Surgical wound infections, Thyroid function tests.

Intraocular Pharmacokinetics of Povidone-Iodine and Its Effects on Experimental Staphylococcus epidermidis Endophthalmitis.

PURPOSE: The purpose of this study was to investigate the pharmacokinetics and safety of intravitreal povidone-iodine (PVI) and its efficacy against experimental Staphylococcus epidermidis endophthalmitis. METHODS: In phase I, forty New Zealand white rabbits were divided into groups I and II and received intravitreal 0.1% and 0.3% PVI, respectively. Electroretinography (ERG) and histologic examinations were conducted at baseline, 6, and 12 hours. Half-life was determined using high-performance liquid chromatography. In phase II, after the induction of S. epidermidis endophthalmitis, 0.1% and 0.3% PVI were injected intravitreally once in groups A and B and three times every second day in groups C and D (n = 10 in each group). Electroretinographs, histologic examinations, and vitreous cultures were conducted on day 14. RESULTS: Electroretinography and histologic examinations did not reveal any notable retinal damage in phase I in either group. Half-lives were 3.27 and 3.58 hours in groups I and II, respectively. In phase II, all groups demonstrated marked improvement, compared to controls. Bacterial growth was found in four eyes in group A (20, 60, 60, and 70 colony forming units [CFU]) and in three eyes in group B (20, 40, and 60 CFU) but not in those belonging to groups C and D at day 14. Retinal damage with lymphocyte infiltration in the inner retinal layers was more common in groups A and B than in groups C and D. CONCLUSIONS: Half-life of PVI was approximately 3 hours in the vitreous. Repeated injection of intraocular PVI, even at low concentrations, is most likely to be effective for the treatment of bacterial endophthalmitis.

Antimicrobial functionalization of bacterial nanocellulose by loading with polihexanide and povidone-iodine.

Bacterial nanocellulose (BNC) is chemically identical with plant cellulose but free of byproducts like lignin, pectin, and hemicelluloses, featuring a unique reticulate network of fine fibers. BNC sheets are mostly obtained by static cultivation. Now, a Horizontal Lift Reactor may provide a cost efficient method for mass production. This is of particular interest as BNC features several properties of an ideal wound dressing although it exhibits no bactericidal activity. Therefore, BNC was functionalized with the antiseptics povidone-iodine (PI) and polihexanide (PHMB). Drug loading and release, mechanical characteristics, biocompatibility, and antimicrobial efficacy were investigated. Antiseptics release was based on diffusion and swelling according to Ritger-Peppas equation. PI-loaded BNC demonstrated a delayed release compared to PHMB due to a high molar drug mass and structural changes induced by PI insertion into BNC that also increased the compressive strength of BNC samples. Biological assays demonstrated high biocompatibility of PI-loaded BNC in human keratinocytes but a distinctly lower antimicrobial activity against Staphylococcus aureus compared to PHMB-loaded BNC. Overall, BNC loaded with PHMB demonstrated a better therapeutic window. Moreover, compressive and tensile strength were not changed by incorporation of PHMB into BNC, and solidity during loading and release could be confirmed.

Povidone iodine skin absorption: an ex-vivo study.

Povidone iodine is a water-soluble complex used to disinfect the skin surface and it exerts prolonged germicidal action against a broad spectrum of germs. Indeed, it is often applied on burned skin, large wounds, deep tissues or mucosa. Notably some surgical hand-scrub solutions, which are considered safe antiseptics, contain large amounts of iodine that can be absorbed by skin. The aim of present study was to study the skin absorption of iodine after the application on the skin of povidone-iodine solution, used by health care workers during surgical procedure. We use Franz diffusion static cells with human skin. After 24h from the beginning of our measurement the iodine concentration in the receiving compartment was 11.59±6.3µg/cm(2). The medium flux calculated was 0.73±0.33µg/cm(2)/h with a lag time of 8.9±1.5h. These in vitro results confirmed that povidone iodine could pass through the skin in a relevant amount that can explain the clinical findings in burned or surgically treated patients. In professional use the repetitive contact with povidone iodine, also as soap, can cause iodine skin permeation that must be considered when the washing procedures are repeated more than 20 times a day.

Systemic iodine absorption associated with the use of preoperative ophthalmic antiseptics containing iodine.

BACKGROUND: Polyvinylpyrrolidone-Iodine (PVP-I) is routinely used as preoperative antiseptic during ophthalmic surgery. Iodine absorption from iodine-containing antiseptics can lead to the development of thyroid disorders. Therefore, a quantitative measurement of iodine absorption from these antiseptics was performed in patients undergoing elective cataract surgery. METHODS: This study enrolled 241 patients to evaluate systemic iodine absorption after exposure to conjunctival and/or periorbital 1.25% and 10% PVP-I compared to an iodine-free antiseptic. RESULTS: All patients who received the 10% PVP-I regardless of the application site showed a 1.2-1.5-fold increase in urinary iodine excretion after 24 h (p = 0.01). In 17 out of 110 (15.5%) patients in whom 10% PVP-I was used, the critical threshold of urinary iodine excretion as defined by WHO (>300 µg/L) was exceeded. In contrast, no significant ioduria was observed with the use of 1.25% PVP-I except in patients after 48 h (p = 0.01) and with a concurrent conjunctival and periorbital application. The proportion of the excreted iodine in urine ranged from 0.24% to 1.77%. No correlation was found between the total applied concentration of iodine and the amount excreted in urine. CONCLUSION: Based on our findings, we believe that the use of 10% PVP-I as preoperative ophthalmic antiseptic should undergo further clinical evaluation in regard to its impact on thyroid function. Conjunctival or periorbital application of 1.25% PVP-I does not result in significant ioduria.

Clearance of topically-applied PVP-iodine as a solution or gel in periodontal pockets in men.

OBJECTIVES: The aim of the study was to investigate the clearance of PVP-iodine applied as a gel or solution in periodontal pockets. METHODS: Teeth of 12 subjects with at least eight periodontal pockets of ≥5 mm probing depth were isolated with a rubber dam to allow contamination-free access to the pockets. In each subject, three pockets were filled with PVP-iodine gel (10%) and three with PVP-iodine solution (10%). One pocket of each subject without iodine application served as a negative control. The treatment allocation was assigned randomly. Any excess material was removed subsequently. After 1, 5 and 15 min, a paper point was used to collect the sulcus liquid and the concentration of PVP-iodine was chemically determined. In addition, PVP-iodine gel was administered into 12 periodontal pockets immediately after sub-gingival ultrasound debridement and the concentration of PVP-iodine was determined after 1 min. RESULTS: Descending concentrations of PVP-iodine were determined at 1, 5 and 15 min after the application. No PVP-iodine was found in the pockets serving as negative controls. The mean concentrations of the gel and solution were 6.14 µg/ml and 4.44 µg/ml (1 min; p ≥ 0.028), 3.20 µg/ml and 1.44 µg/ml (5 min; p ≥ 0.126), 0.69 µg/ml and 0.23 µg/ml (15 min; p ≤ 0.019), respectively. In the pockets with previous debridement the mean concentration was 1.68 ± 1.97 µg/ml. CONCLUSION: The application of PVP-iodine gel in periodontal pockets allows a prolonged remnant effect as compared to that of the solution formula.

Critical evaluation of cadexomer-iodine ointment and povidone-iodine sugar ointment.

Topical iodine forms are used for infected and necrotic pressure ulcers. Despite antimicrobial advantages several potential disadvantages were observed with controversial results. To clarify the controversy, the reactivity of povidone-iodine (PI) sugar ointment and cadexomer-iodine (CI) ointment toward biological components was investigated. L-Tyrosine as a component of proteins and egg lecithin as a component of lipid membranes were reacted with forms of iodine. Furthermore, water absorption abilities of ointments were investigated. The reactions of PI sugar ointment and CI ointment with L-tyrosine were reversely dependent on iodine concentrations. CI ointment reacted with lecithin in an iodine concentration dependent manner, while PI sugar ointment reacted with lecithin in an iodine concentration independent steady manner. However, at the clinically relevant iodine concentration (0.1, w/v%) PI sugar ointment reacted efficiently with L-tyrosine and less efficiently with lecithin, while CI ointment reacted efficiently with lecithin and less efficiently with L-tyrosine. Water absorption rate constant was 29.9 mg/cm(2)/min(0.5) for PI sugar ointment and 15.3 for CI ointment. Water absorption capacity per weight over 24 h was 26% forPI sugar ointment and 76% for CI ointment [corrected]. These results suggest that PI sugar ointment and CI ointment have different characteristics for iodine reactivity and water absorption.

Use of povidone-iodine during the first trimester of pregnancy: a correct practice?

Povidone-iodine (PVP-I) has been widely used as an antiseptic agent during invasive procedures for prenatal diagnosis. Women have been reported of thyroid dysfunction after simple exposure to PVP-I. We studied the effect on thyroid function and urinary iodine excretion after a single topical application of PVP-I in 31 women who had a miscarriage during the first trimester of pregnancy. PVP-I is absorbed through the skin and the vaginal mucosa, resulting in a sudden increase in the urinary excretion of iodine and a short-term variation in concentrations of thyroid hormones in maternal serum. This metabolic effect could have consequences for the embryo and the fetus during crucial stages of development.

Maternal and neonatal urinary iodine excretion and neonatal TSH in relation to use of antiseptic during caesarean section in an iodine sufficient area.

AIM: To evaluate the influence of topical iodine-containing antiseptics on neonatal TSH in full-term infants born by Caesarean section in an iodine sufficient area. POPULATION AND METHODS: Urinary iodide excretion (UIE) was estimated in 86 mothers on the second day after delivery by Caesarean section and their 86 full-term neonates. The mothers were divided into two groups according to the use of antiseptic to prepare Cesarean sections: 42 mothers who were prepared with povidone-iodine (Isosept, Bosnalijek) comprised the study group, and 47 mothers who were prepared with alcoholic solution (Skinsept color, Ecolab) formed the control group. Neonatal TSH was measured in whole blood drawn between day 3 and 5 of life, spotted on filter paper using a sensitive fluorometric assay (Delfia). RESULTS: Maternal and neonatal UIE were significantly higher (p < 0.05) in the study group compared to the control group. No significant difference was found for neonatal TSH. CONCLUSION: Our data suggest that perinatal iodine exposure of full-term neonates who were born by Caesarean section in an iodine sufficient area did not influence neonatal TSH, although median UIE was higher, suggesting optimal iodine intake during pregnancy. Further research is needed to define a critical value of urinary iodine concentrations in full-term neonates in an iodine sufficient area that may lead to the impairment of thyroid function.

Prospective study to determine the penetration of iodide into the anterior chamber following preoperative application of topical 1.25% povidone-iodine.

BACKGROUND: Povidone-iodine is currently the agent of choice for pre-operative antisepsis in ophthalmology. Due to experimental and analytical constraints, iodine absorption into the anterior chamber (AC) has not yet been studied. However, knowledge of the details of iodine transfer into the aqueous humor (AH) is critical for risk assessment of local and/or systemic side effects METHODS: Following a 2-min antisepsis with 1.25% povidone-iodine, the AC of eligible cataract patients was penetrated with a 26-gauge cannula prior to any other intraocular manipulation. To distinguish between the iodine absorbed into the AC and that remaining in the hypodermic delivery syringe, we studied three different groups of specimens: (i) AH from the AC (n=19); (ii) Ringer's solution aspirated through the cannula after penetration into and immediate withdrawal from the AC without subsequent decontamination (n=8); and (iii) Ringer's solution aspirated through the cannula after penetration into and immediate withdrawal from the AC, and subsequent decontamination of its outer surface (n=5). Patients with pre-operative epithelial defects were excluded from the study. To measure iodine absorption, iodide levels in samples were determined chromatographically (ion-pair chromatography) and electrochemically (gold electrode). RESULTS: There was no difference (P=0.815) between detectable amounts of iodide in groups I and II (median: 24.0 microg/dl and 28.9 microg/dl, respectively). Only group III (median: 5.2 microg/dl) showed a statistically significant lower level of iodide than did groups I or II (P=0.019 and P=0.011, respectively). CONCLUSIONS: A healthy ocular surface behaves as a barrier to the penetration of iodine into the AC. Any detectable iodide in the AH after antisepsis should therefore be considered harmless.

Systemic iodine absorption after preoperative antisepsis using povidone-iodine in cataract surgery-- an open controlled study.

After preoperative conjunctival and periorbital antisepsis with povidone-iodine (PVP-I), the systemic absorption of iodine after cataract surgery was measured to evaluate the risk of thyroid side effects. Five different combinations of PVP-I alone or in combination with PVP-I-free antiseptics were applied to the conjunctiva and periorbital skin. An iodine-free product served as control. Iodide and creatinine in urine were analyzed before intervention and 24 and 48 h postoperatively. Depending on the concentration and application site, 0.3-4.5% of the total applied iodine or 3.6-45.4% of the free iodine were absorbed. The range of urine iodine excretion was between 11.7 and 71.0 mug iodine/g creatinine, depending on the PVP-I concentration and the site of application. The increase in iodine excretion was significant at 24 h postoperatively in trials receiving PVP-I both periorbitally and conjunctivally, depending of the concentration used. Because the iodine absorption is only slight and of doubtful clinical relevance, presurgical conjunctival antisepsis can be achieved with 1.25% PVP-I; so far clinically manifest anamnestic thyroid disorders are excluded. Presently, periorbital skin antisepsis with PVP-I cannot be recommended until data on thyroid metabolism in the population have been collected and evaluated, especially in a region currently or previously deficient in iodine.

Transcutaneous iodine absorption in adult patients with thyroid cancer disinfected with povidone-iodine at operation.

Povidone-iodine is used as disinfection in patients undergoing many kinds of operations. Several cases of thyroid dysfunction induced by transcutaneous absorption of povidone-iodine have been reported in small infants. However, transcutaneous absorption was not clearly reported in adults. The aim of this study was to assess transcutaneous absorption of iodine in patients who received single topical application with povidoneiodine and serial changes of urinary iodine excretion under the condition with a simple iodine-restricted diet in Japan, an iodine-sufficient area. Sixty-eight patients with thyroid carcinoma undergoing total thyroidectomy received single skin disinfection with either povidone-iodine (group A; n = 47) or chlohexidine gluconate, a noniodine containing biguanide (group B; n = 21). In group A, urinary iodine excretion on the first day after operation increased up to 7 times that of the preoperative value. The amounts of urinary iodine correlated positively with operating time. Increased urinary iodine, however, returned to preoperative values on the third or fifth day after operation. In group B, there was no increase in urinary iodine excretion and urinary iodine excretion was ranged from 54 to 193 microg/g of creatinine on the third day of operation. In conclusion, a large amount of povidone-iodine was absorbed through healthy skin even in adults. This may possibly interfere with scintigraphy or radioactive iodine treatment, or cause thyroid disinfection in susceptible patients.

Production and characterization of biodegradable Povidone-iodine microsphere as a intramammary disinfectant.

Microspheres composed of biocompatible, biodegradable poly DL-lactide-co-glycolide (DL-PLGA) and Povidone-iodine were evaluated as an intramammary disinfectant delivery system in vitro prior to infusion into mammary glands. Microsphere was prepared by solvent evaporation method and particle size, morphology and in vitro release kinetics were examined. The microspheres were ranged in size from 25 microm to 155 microm (mean diameter = 65.7 microm). Povidone-iodine was dispersed on the surface of microsphere and microsphere was spherical in shape with a smooth surface. The yield of microsphere was 57.3% and the encapsulation efficiency was 69.6%. In in vitro release study, a burst effect (50.9%) was observed during the first two days and a sustained release then continued for the next 28 days. Results of the present study demonstrated that microsphere have the potential for new intramammary disinfectant formulations that can provide increased efficacy of therapy against mastitis pathogens.

New aspects of the tolerance of the antiseptic povidone-iodine in different ex vivo models.

Investigating new possibilities for the application of 1% (v/v) iodophors, povidone-iodine (PVP-I) was better tolerated in the HET-CAM or explant test than 1% (w/v) silver nitrate or tetracycline. After application to the eye, at least 2.6% of used iodine were adsorbed. Therefore PVP-I is more effective than silver nitrate or erythromycin, meaning a possible alternative for the prevention of ophthalmia neonatorum. PVP-I is more active against methicillin-resistant Staphylococcus aureus (MRSA) in a human ex vivo skin model, which results in a complete eradication of S. aureus in the nasal cavity of volunteers after 2 daily applications and will be better tolerated by human nasal cilial epithelium than chlorhexidine. Having the same clinical tolerance as mupirocin, PVP-I is a useful alternative for the antiseptic therapy of germ carriers of MRSA. The synthesis of proteoglycans in articular cartilage of bovine sesamoid bones was increased after application of 5% (v/v) PVP-I without any increase in catabolism revealing possibilities for the use as irrigation solution in the joint.

Thyroid function in nurses: the influence of povidone-iodine hand washing and gargling.

The effect of povidone-iodine (PVP-I) hand washing and gargling on thyroid function was assessed. In 16 nurses using PVP-I products and 16 control subjects, serum inorganic iodine levels and thyroid functions were investigated. The status of PVP-I use was also surveyed in the nurses. Clinical symptoms considered to be attributable to thyroid dysfunctions were seen in none of the subjects, nor was a goiter observed in any of the subjects. In nurses, serum inorganic iodine levels were slightly increased as compared to those in the control subjects, although the difference was not significant. The iodine incorporated during working hours of nurses appears to be attributable to gargling rather than to hand washing. The long-term use of PVP-I for gargling should be avoided by (1) people with a high risk of developing thyroid dysfunction due to the excessive intake of iodine, (2) pregnant women and (3) breast-feeding mothers.